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Evolution of the mammalian middle ear and jaw: Adaptations and novel structures

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Having three ossicles in the middle ear is one of the defining features of mammals. All reptiles and birds have only one middle ear ossicle, the stapes or columella. How these two additional ossicles came to reside and function in the middle ear of mammals has been studied for the last 200 years and represents one of the classic example of how structures can change during evolution to function in new and novel ways. From fossil data, comparative anatomy and developmental biology it is now clear that the two new bones in the mammalian middle ear, the malleus and incus, are homologous to the quadrate and articular, which form the articulation for the upper and lower jaws in non-mammalian jawed vertebrates. The incorporation of the primary jaw joint into the mammalian middle ear was only possible due to the evolution of a new way to articulate the upper and lower jaws, with the formation of the dentary-squamosal joint, or TMJ in humans. The evolution of the three-ossicle ear in mammals is thus intricately connected with the evolution of a novel jaw joint, the two structures evolving together to create the distinctive mammalian skull.
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REVIEW
Evolution of the mammalian middle ear and jaw:
adaptations and novel structures
Neal Anthwal,
1
Leena Joshi
2
and Abigail S. Tucker
2
1
Division of Developmental Neurobiology, MRC National Institute for Medical Research, London, UK
2
Department of Craniofacial Development and Stem Cell Biology, King’s College London, Guy’s Hospital, London, UK
Abstract
Having three ossicles in the middle ear is one of the defining features of mammals. All reptiles and birds have
only one middle ear ossicle, the stapes or columella. How these two additional ossicles came to reside and func-
tion in the middle ear of mammals has been studied for the last 200 years and represents one of the classic
example of how structures can change during evolution to function in new and novel ways. From fossil data,
comparative anatomy and developmental biology it is now clear that the two new bones in the mammalian
middle ear, the malleus and incus, are homologous to the quadrate and articular, which form the articulation
for the upper and lower jaws in non-mammalian jawed vertebrates. The incorporation of the primary jaw joint
into the mammalian middle ear was only possible due to the evolution of a new way to articulate the upper
and lower jaws, with the formation of the dentary-squamosal joint, or TMJ in humans. The evolution of the
three-ossicle ear in mammals is thus intricately connected with the evolution of a novel jaw joint, the two struc-
tures evolving together to create the distinctive mammalian skull.
Key words: evolution mammals; jaw joint; middle ear.
Introduction
The middle ear ossicles in mammals sit in an air-filled cavity
and bridge the gap between the external and inner ear.
Vibrations in the tympanic membrane (ear drum) are picked
up by the manubrium of the malleus and transferred to the
incus and stapes, which then conducts the vibrations to the
inner ear via the oval window (Fig. 1B,D). Defects in this
process lead to conductive hearing loss. In birds and rep-
tiles, a single ossicle spans the air-filled middle ear cavity,
transferring vibrations from the external to inner ear. In
birds this ossicle is known as the columella auris, while in
reptiles it is known as the stapes (Fig. 1A,C).
The mammalian middle ear ossicles are housed in the
auditory bulla, a bony capsulethatprotectstheearand
defines the cavity. The bulla is made of a number of bones,
including the tympanic ring that supports the tympanic
membrane. The tympanic ring is a membranous bone that
forms in close association with Meckel’s cartilage and the
malleus. The smaller gonial bone lies in between the tym-
panic ring and the malleus and has an important role as an
investing bone for the malleus. The malleus is therefore a
compound bone with a dual origin from endochondrial
ossification and from invasion of bone from the gonial.
As reptiles and birds only have one ossicle, homologous
to the mammalian stapes, the homologous skeletal ele-
ments to the malleus, incus, tympanic ring and gonial have
been a subject of much discussion. Where did these extra
ossicles and bones come from?
In 1837, Reichert proposed that the malleus and incus
were homologous to the articular and quadrate of the
non-mammalian jaw joint based on anatomical compari-
sons (Reichert, 1937). In 1912, Gaupp extended Reichert’s
theory and described the development of a primary jaw
joint between the malleus and incus and a secondary
jaw joint between two membraneous bones, the squa-
mosal and dentary, that wasuniquetomammals(Gau-
pp, 1912). Other theories have been proposed and
rejected, but Reichert’s theory has subsequently been
supported by a wealth of information from the fossil
record, from developmental biology and molecular biol-
ogy and from the study of marsupials. Together,
research in these areas has produced a united theory of
the steps and possible mechanisms involved in creating
the unique mammalian ear and jaw.
Correspondence
Abigail S. Tucker, Department of Craniofacial Development and
Stem Cell Biology, King’s College London, Floor 27 Guy’s Tower,
Guy’s Hospital, London Bridge, London SE1 9RT, UK.
E: abigail.tucker@kcl.ac.uk
Accepted for publication 14 May 2012
Article published online 11 June 2012
ªª 2012 The Authors
Journal of Anatomy ªª 2012 Anatomical Society
J. Anat. (2013) 222, pp147–160 doi: 10.1111/j.1469-7580.2012.01526.x
Journal of Anatomy
Evidence from developmental biology
Meckel’s cartilage appears as two rods of hyaline cartilage
that traverse the lateral aspect of the mandible. In non-
mammalian vertebrates the most proximal part of Meckel’s
forms the articular and quadrate (or palatoquadrate). These
are endochondrial bones between which the jaw joint
forms, articulating the upper and lower jaw. From fate-
mapping studies between quail and chick embryos the artic-
ular part of Meckel’s and the quadrate have been shown to
be derived from the first pharyngeal arch (Couly et al. 1993;
Kontges & Lumsden, 1996). The retroarticular process that
develops proximally to the articular, and the body of the
columella are derived from the second pharyngeal arch.
The quadrate and articular are initially derived from a single
cartilaginous condensation that subdivides to form the two
skeletal elements separatedbythejawjoint(Wilson&
Tucker, 2004). If the malleus and incus are homologous to
the articular and quadrate, we would expect a similar
pattern of embryonic development.
Just as observed with the articular and quadrate, the
malleus and incus are endochondrial bones initially united
as a single cartilaginous condensation, which subdivides
into the two ossicles (Amin & Tucker, 2006). In contrast, the
stapes is derived from a separate condensation that grows
towards the incus to form a joint. Like the articular and
quadrate, the malleus and incus form from the posterior
part of Meckel’s cartilage and the malleus, like the articular,
remains attached to Meckel’s during much of embryonic
development, forming a direct connection between mandi-
ble and middle ear (Fig. 2).
The incus retains a thin connective tissue link, visible by
histology, to the ala temporalis, which is thought to be
homologous to the ascending process of the palatoqua-
drate (Presley & Steel, 1978). In the mouse the cartilage con-
nection between the jaw and ear only breaks down
postnatally, starting at around P2, with the transformation
of Meckel’s cartilage next to the malleus into the spheno-
mandibular ligament. This breakdown of Meckel’s cartilage
is an important step in mammals as it allows functional
separation of the ear from the jaw, and it will be discussed
in more detail later. In non-mammalian species, in contrast,
Meckel’s cartilage remains continuous, forming a core sup-
port for the membraneous bones that ossify along its
length, from symphysis to articulation point.
Fate-mapping studies using a Hoxb1-cre reporter mouse
have shown that the processus brevis at the bottom of the
malleus and the stapes are second arch-derived (O’Gorman,
2005). The fact that the mammalian stapes and the bird col-
umella are both second arch-derived again strengthens the
homology between these two ossicles. This result also indi-
cates that the processus brevis on the end of the malleus is
AB
CD
Fig. 1 Middle ear ossicles in mammals and birds. (A) Frontal section through the developing middle ear of a chick showing the columella (c)
spanning the gap between the external and internal ear at E (embryonic day) 6. (B) Sagittal section through the developing murine middle ear
showing three ossicles, the malleus (M), incus (I) and stapes (S), between the external and inner ear at E15.5. (C,D) MicroCT images. (C) Footplate
of the columella (c) inserting into the oval window of the inner ear in an adult partridge. The shaft and footplate of the columella are ossified
while the extracolumella arms, which interact with the tympanic membrane, remain cartilaginous and are not picked up by microCT. (D) Three
ossicles form a chain in a P (postnatal day) 14 mouse.
ªª 2012 The Authors
Journal of Anatomy ªª 2012 Anatomical Society
The mammalian middle ear and jaw, N. Anthwal et al.148
homologous to the second arch-derived retroarticular pro-
cess on the end of the articular. This is an intriguing finding
as from classical comparative anatomy and fossil data it had
been suggested that the retroarticular process was homolo-
gous to the manubrium of the malleus (Kermack & Musset,
1983; Allin & Hopson, 1992) . The fate-mapping experi-
ments, however, argue strongly against this and suggest
that the manubrium is a novel mammalian structure with-
out a homologue in birds and reptiles.
Reichert’s theory has also been backed up by analysis of
gene expression. For example, Bapx1 is a jaw joint marker,
expressed in the developing articular-quadrate joint in
birds, fish and reptiles (Miller etal.2003;Wilson&Tucker,
2004) (Fig. 3A–D). In mammals, however, Bapx1 is found
associated with the malleal-incudo joint in the developing
middle ear (Tucker et al. 2004) (Fig. 3E,F). The malleus artic-
ular and incus quadrate therefore share a common devel-
opmental history, tissue origin, and gene expression
pattern (schematised in Fig. 4).
Developmental biology can also help identify the homol-
ogous elements for the associated membranous bones of
the ear. The tympanic ring and gonial, for example have
been suggested to be homologous to the angular bone
and prearticular, respectively. Again, by following the posi-
tion and relative timing of these bones as they develop,
clear homologies can be identified (Fig. 2). Bapx1 is also
expressed around these membraneous bones in both chick
and mouse (Tucker et al. 2004).
The malleus and incus ossify relatively early in develop-
ment, fixing their size in contrast to the growing cranium
and mandible. In this way the ossicles remain small while
the head grows. This negative allometry can be followed
clearly in marsupial neonates, as the malleus and incus
change from a jaw-supporting to hearing role (as outlined
in Luo, 2011). It has been suggested that this early ossifica-
tion had a central role in changing the relative size of the
malleus and incus with respect to the head but might have
also led to the posterior displacement of these ossicles nec-
essary for isolation of the ear from the jaw.
Evidence from mouse mutants
Anumberofmousemutantshave been created which
result in re-shaping of the middle ear region, leading to the
development of dysmorphic ossicles, or even transforma-
tions of ossicle type due to a change in patterning of the
mandible and maxilla. In Dlx5 6double knockout mice the
mandible is transformed intotheidentityofthemaxilla,
leading to the formation of rugae (palatal ridges) and
vibrissae development on the lower jaw (Depew et al.
2002). The endothelin pathway acts upstream of the Dlx
genes and a similar transformation of jaw identity is
observed after knockout of theendothelinreceptor(Ednra;
Clouthier et al. 1998; Ozeki et al. 2004; Ruest et al. 2004). In
both Dlx and endothelin receptor mutants the tympanic
ring and gonial are lost and the malleus is dysmorphic, pos-
sibly showing a transformation to an incus morphology
(Ozeki et al. 2004; Depew et al. 2005). An equally dramatic
reverse transformation of maxilla to mandible is observed
when the endothelin receptor is made constitutively active
BCA
EF
D
Fig. 2 Comparison of membranous bone ossification in the middle ear and jaw joint. Alcian Blue and Alizarin Red-stained skeletal preparations.
(A–C) Development of the cartilages and bones of the murine middle ear, side view. (D–F).Development of the cartilages and bones of the chick
jaw joint, dorsal view. (A) Formation of the malleus and incus at E14.5. The malleus develops at the proximal end of Meckel’s cartilage. There is
no bone ossification at this stage. (B) Ossification of the tympanic ring at the base of the malleus at E16.5. (C) Ossification of the gonium in
between the malleus and tympanic ring at birth (P0). (D) Formation of the jaw joint between the articular and the quadrate at E7. The articular
lies at the proximal end of Meckel’s cartilage. (E) Ossification of the angular under the articular and Meckel’s at E9. (F) Ossification of the
prearticular next to the angular at E13. I, incus; M, malleus; Me, Meckel’s cartilage; Ty, tympanic ring; G, gonium; A, articular; Q, quadrate; An,
angular; P, prearticular. (Chick images taken from Tucker et al. 2004).
ªª 2012 The Authors
Journal of Anatomy ªª 2012 Anatomical Society
The mammalian middle ear and jaw, N. Anthwal et al. 149
(Sato et al. 2008). In this knockin mouse, Meckel’s cartilage
from the two mandibles meet to form a middle ear with
two tympanic rings, and two gonials and a possible duplica-
tion of the malleus (Sato et al. 2008). These mutants
strengthen the idea that the joint between the incus and
malleus is the pivotal point between the upper and lower
jaws in the mouse; thus although the articulation site has
moved, the genetic regulation of upper and lower fate is
still controlled around the primary jaw articulation. In
Hoxa2 mutants, the second arch is transformed into a proxi-
mal first arch, and the second arch-derived structures such
as the stapes and Reichert’s cartilage are missing. In their
place, an ectopic malleus, incus and tympanic ring form
(Gendron-Maguire et al. 1993; Rijli et al. 1993). In addition,
an ectopic cartilage was found connected to the incus that
was suggested to be a palatoquadrate, the homolog of the
incus in primitive vertebrates (Rijli et al. 1993). A similar
ectopic palatoquadrate has been observed in Dlx2 mutants
(Qiu et al. 1995). These mutants were therefore proposed
to show a skull pattern more reminiscent of the basic synap-
sid skull of a pre-mammalian ancestor. It has been argued,
however, that these ectopic cartilages do not represent true
atavisms and are secondary consequences of disruptions in
cell specification, migration and or differentiation (Smith &
Schneider, 1998). Such changesmightcausethechondrica-
tion of the connective tissue thread that links the incus to
the ala temporalis. The identity and significance of such
ectopic cartilages are therefore unclear. In the Hoxa2
knockout, the ectopic middle ear elements develop as
mirror image versions of the normal first arch-derived mid-
dle ear skeletal structures and fuse with them at the point
where the first and second arch crest normally meet. For
example, the ectopic malleus fuses with the normal malleus
at the position of the second arch-derived processus brevis,
which is lost (O’Gorman, 2005). A distinct origin for the
processus brevis, relative to the rest of the malleus, is high-
lighted in the Msx1 mutant, where the first arch-derived
body of the malleus and manubrium are normal but the
second arch processus brevis is lost (Satokata & Maas, 1994).
Other mutants show loss of specific regions of the middle
ear, shedding light on how identity of the ossicles might be
regulated. For example, the incus is specifically lost in the
Emx2 mutant, leaving the malleus and incus relatively unaf-
fected (Rhodes et al. 2003). Emx2 is expressed within and
around the developing incus (Amin & Tucker, 2006). Given
the distinct role for Emx2 in the incus, it would be predicted
that in a non-mammalian gnathostome Emx2 would be
expressed in the quadrate palatoquadrate. Interestingly
AB
CD
EF
Fig. 3 Conservation of Bapx1 expression between the quadrate and
articular and malleus and incus in a bird, reptile and mammal. Sagittal
sections through the developing jaw joint in (A,B) Chick and (C,D)
Python, and through the middle ear in the mouse (E,F). (A,C,E)
Histology sections. (B,D,F) Serial sections in situ hybridization for
Bapx1 (silver grains). Arrows point to joint. A, articular; Q, quadrate;
Me, Meckel’s cartilage; M, malleus; I, Incus.
Fig. 4 Schematic of a chick and mouse head during late development. Homologous structures are shown in the same colour.
ªª 2012 The Authors
Journal of Anatomy ªª 2012 Anatomical Society
The mammalian middle ear and jaw, N. Anthwal et al.150
Emx2 has been shown to be expressed in distinct regions in
the developing pharyngeal arches in dogfish and Xenopus
embryos (Derobert et al. 2002; Galli et al. 2003). Whether
the expression domain corresponds to the palatoquadrate
during later development, however, is unclear, with expres-
sion in the dogfish suggested to be in the mesoderm rather
than the neural crest (Derobert et al. 2002).
Evidence from fossils
Although somewhat sparse, the fossil evidence for the evo-
lutionary transition of the articular-quadrate jaw articula-
tion to the malleal-incodal middle ear joint is amongst the
most complete of any anatomical transition (as reviewed
extensively in Luo, 2011). The emergence of mammal-like
reptiles (mamalliforms) occurred in the cynodont synapsid
lineage, a group that gave rise to modern mammals as well
as extinct ancestors and closely related species (Luo, 2011).
In fact all extant mammals aredescendantsofjustthree
Mesozoic lineages (placental, monotreme and marsupial)
from a compliment of more than 20 extinct mammalian lin-
eages (Kielan-Jaworowska et al. 2004; Benton, 2005).
In such transitional fossils it is clear that the first step in
the process of formation of a mammalian-like ear and jaw
was the development of a double jaw joint, that is, two side
by side joints, one between the articular and the quadrate
and the other between the dentary and the squamosal. An
extended upward dentary, which perhaps provided a step
towards formation of such a second joint, has been
observed in the non-mammaliansynapsids,Scymnognathus
and Ictidopsis (Hall, 2005; Kemp, 2005). In tritheledontids
and brasilodontids, two advanced mammal-like synapsid
groups, the dentary has a lateral ridge that contacts the
ventral side of the squamosal forming a functional hinge
but does not have a well developed articulation (Luo,
2011). A clear double jaw joint is evident in the prototypical
basal mammaliform Morganucodon from the Jurassic. In
synapsids such as Morganucodon the articular-quadrate
joint is attached to both an ossified Meckel’s cartilage and
dentary bone (Kermack et al.1981).Morganucodonhas
conical cusps on its teeth, with numerous accessory cusps,
and importantly the teeth are elongated along the line of
the jaw with multiple roots. Unlike the teeth of reptiles,
these teeth would have functioned as a shearing mecha-
nism. The formation of a double joint may have had the
advantage of providing resistance against the forces
produced by this searing dentition, which would have
introduced a twisting motion to the jaw. Such a twisting
would result in a tendency to dislocate the jaw articulation,
prevented by the presence of the double articulation
(Kermack, 1972; Crompton & Hylander, 1986; Kemp, 2005).
The advent of a double jaw joint was therefore directly
linked to a change in tooth shape and change in mode of
mastication. A similar double jaw joint has been described
in Kuehneotherium, which has been suggested to be the
ancestor of placental and marsupial mammals, while Mor-
ganocodon has been suggested to be related more closely
to monotremes. In both cases, however, the mandible is a
compound structure and the Q-A joint pronounced.
The postdentary middle ear bones (angular, prearticular)
in early mammaliforms are housed in a trough in the den-
tary bone. In many fossils the small middle ear ossicles and
associated bones are lost but the trough in the dentary is
taken as evidence of their existence and attachment to the
dentary. Such a postdentary trough is observed in Morgan-
ucodon. In a similar manner, the presence of a Meckel’s
groove on the dentary has been used as evidence of a per-
sistent Meckel’s cartilage.
The next step after evolution of a double articulation
appears to have been detachment of the postdentary
bones from the dentary, as evidenced by lack of a
postdentary trough. These postdentary bones would
have still been connected to the jaw via an ossified
Meckel’s cartilage. It is important to note that lack of a
postdentary trough does not automatically mean that
the middle ear bones were detached from the jaw (Ji
et al. 2009). Recently, an unambiguous example of a
transitionary form was described in the form of Liaocon-
odon, an eutriconodont mammal from the early creta-
ceous. Here, the malleus and ectotympanic are preserved
and detached from the dentary while maintaining their
connection to an ossified Meckel’s cartilage. An ossified
Meckel’s is also found in several gobiconodontids, the
Spalacotheroid Maotherium and the eutriconodont Yano-
conodon (Wang et al. 2001; Luo et al. 2007; Ji et al.
2009). Detachment therefore appears to have occurred
independently in a number of different lineages during
evolution and can be regarded as a frequent homoplasy
(Luo, 2011). It is thought that Meckel’s was ossified to
provide a support for the middle ear ossicles, before
their connection to the cranium (Meng et al. 2011). The
displacement of the malleus and incus from the lower
jaw indicates their increasing specialisation as auditory
ossicles, though not unaffected by chewing, a conse-
quence of the fusion to an ossified Meckel’s cartilage.
The final step in formation of the definitive mammalian
middle ear appears to have been a breakdown of Meckel’s
cartilage, so that the ear is no longer physically connected
to the jaw. This is linked with support for the ear by connec-
tion to the cranium, with the formation of the auditory
bulla. Such a situation is observed in Hadrocodium, which
does not have a postdentary trough or Meckel’s groove.
The only jaw articulation is between the dentary and squa-
mosal and the ear would appear to be completely free of
the jaw. Interestingly, Hadrocodium has a large brain case,
indicating that indeed an increase in brain size might have
influenced the separation of the middle ear bones from the
jaw (Luo et al. 2001), agreeing with the proposal of Rowe
(1996). In Repenomamus, however, the brain case is small,
disagreeing with the theory that detachment of the postd-
ªª 2012 The Authors
Journal of Anatomy ªª 2012 Anatomical Society
The mammalian middle ear and jaw, N. Anthwal et al. 151
entary bones from the jaw was driven by expansion of the
brain (Wang et al. 2001).
In birds and reptiles the tympanic membrane (ear drum)
is supported by the quadrate. As this bone reduced in size
and became incorporated into the middle ear, a new sup-
port was necessary for the tympanic membrane. From the
fossil record it appears that the angular bone took over this
role, transforming from a lower jaw support to the tym-
panic ring. In cynodonts the angular is plate-like, with a
large surface area for receiving sound. Whether the mam-
malian and non-mammalian tympanic membranes are
homologous is still an area of dispute, with discrepancies
involving the position of themusclesinrelationtothe
Eustachian tube indicating that the two ear drums may not
be homologous (reviewed in (Takechi & Kuratani, 2010)).
Evidence from marsupials
Although the fossil record provides clues to the transition it
is often incomplete and relies on a few isolated specimens.
The ideal solution would be to be able to follow the transi-
tion from primary to novel articulation in a living animal.
This is indeed possible in marsupials (Maier, 1987). In marsu-
pials the neonate must be able to suckle at an early develop-
mental stage, prior to the formation of the bones that will
make up the normal mammalian jaw joint. Marsupials,
therefore utilise the joint between the incus and malleus as
their primary jaw joint for the first few weeks after birth
(Muller, 1968) (Fig. 5). A clearsynovialjointbetweenthe
malleus and incus has been reported at postnatal day (P) 3
in the opossum Monodelphis (Filan, 1991). The degree that
this middle ear joint is actually functional in the newborn is
debatable, and much of the suckling action is thought to be
achieved by the flexibility of Meckel’s cartilage (Filan, 1991).
The dentary, squamosal and condylar cartilage then start to
form and a double joint is visible, one between the incus
and malleus and one between the squamosal and dentary.
The connection between the malleus and Meckel’s cartilage
is lost by P20, with the squamosal and dentary taking over
the role of jaw joint. At this stage the malleus and incus are
still relatively large and attached to the brain case but over
the following weeks they become incorporated into the
middle ear (Filan, 1991; Clark & Smith, 1993; Smith, 2006).
During this transition the muscles change, exemplified by
the changing shape and size of the tensor tympani, which
inserts on the malleus. In the opossum neonate at P0, the
cells of the tensor tympani are found in a continuous mass
with the internal pterygoideus (one of the jaw-closing mus-
cles which inserts on the angular process of the dentary).
Both muscles are of a similar size at this time point. As the
malleus and incus shift from their role as support for the
dentary to hearing, the tensor tympani changes from a
large mass of fibres to a small muscle inserting on the mal-
leus, whereas the pterygoid greatly increases in size (Smith,
1994). This change in size represents a change in function
from a major support of the jaw to an ear-drum tensing role
within the middle ear. Marsupials therefore provide a great
resource for following the transition from primary to novel
jaw articulation. The marsupial use of the primary jaw joint
has been cited as an example of ‘von Baer’s recapitulation’,
based on the fact that the marsupial neonate resembles that
of the embryonic condition of mammalian ancestors (Maier,
1990; Sanchez-Villagra et al. 2002).
The secondary jaw joint
Utilisation of the articular, quadrate, angular and prearticu-
lar in the mammalian ear would not be possible without
the evolution of a new jaw articulation between the squa-
mosal and dentary (Fig. 5A). The benefits of the squamosal-
dentary joint, providing a robust, load-bearing articulation
point, have been argued to be the driving force in the evo-
lution of the mammalian ear (Crompton, 1963; Crompton &
Hylander, 1986). In this scenario, supported by the fossil
record, the new jaw joint would have come first, freeing up
the primary jaw joint to play a role in the middle ear as a
secondary consequence. For the successful creation of a
new joint between two membraneous bones (squamosal
and dentary), it was critical that an articulation surface was
created between them. This problem was solved by the
development of a secondary cartilage on the condylar
process of the dentary to create a synovial joint at the jaw
articulation. In humans the squamosal fuses with the tym-
panic, petrosal, styloid process and mastoid to form the
compound temporal bone, and the jaw joint is given the
name temporomandibular joint (TMJ). The TMJ is a sliding
joint made up of the glenoid fossa of the upper jaw, and
condylar of the dentary separated by a disc (Fig. 6A,B). The
ABC
Fig. 5 Jaw joint comparison in the mouse, chick and the marsupial Monodelphis. Skeletal preps. Red – bone stained by Alizarin Red. Blue –
cartilage stained by Alcian Blue. (A) Mouse postnatal day (P) 0. (B) Chick embryonic day (E) 13. (C) Monodelphis P2. Arrows joints to the
articulation point for the upper and lower jaws. Q, quadrate; A, articular; M, malleus; I, incus; S, squamosal; D, dentary.
ªª 2012 The Authors
Journal of Anatomy ªª 2012 Anatomical Society
The mammalian middle ear and jaw, N. Anthwal et al.152
cavity between the condylar and disc (inferior) allows for
rotation of the jaw during initial mouth opening, while the
cavity between the disc and glenoid fossa (superior) allows
for translational (gliding) movement as the jaw opens wide.
The disc develops from the condylar as a sheet of cells that
lift off to create the lower synovial cavity, this process
involving the hedgehog signalling pathway (Shibukawa
et al. 2007; Purcell et al. 2009). The formation of a disc is
therefore only possible due to the initial development of
the condylar. The disc is associated with the discomallear
ligament, which corresponds to a remnant of the lateral
pterygoid muscle, which attaches to the caudal end of Mec-
kel’s cartilage during embryonic development (Ogutcen-
Toller, 1995; Cheynet et al. 2003). In reptiles and birds this
muscle inserts on the quadrato-articular joint. The discomal-
leal ligament provides a connection between the malleus
and jaw, along with the sphenomandibular ligament,
which will be discussed later.Inclinicalcases,wherethe
TMJ fails to form, the malleus and incus take over some of
the role of jaw articulation, these elements therefore
reverting to the role of jawsupport(Herring,1993).
Specialisation of the proximal dentary
The evolution of the squamosal dentary joint has
resulted in a greater level ofcomplexityofthedentary
in mammals compared with non-mammalian tetrapods.
The prototypical tetrapod dentary is a simple tooth-
bearing bone forming one part of the compound man-
dible, along with the angular, surangular, prearticular,
splenial, and coronoid. In contrast, the mammalian den-
tary alone forms the mandible and is highly modular in
nature, taking on all the functions of the membraneous
bones of the lower jaw in non-mammals. The proximal
dentary typically possesses three processes. These are the
joint-forming condylar and two un-opposed processes
which act as muscle attachment sites: the coronoid supe-
rior rostral to the condylar, and the angular, infe-
rior ventral to the condylar (Fig. 6C). These structures are
not homologous to the angular and coronoid process of
the non-mammalian mandible but they serve similar
functional roles. For example, the coronoid process of a
fish and a mammal both act as muscle attachment sites
for the jaw muscles but one is an endochondrial bone
derived from Meckel’s cartilage (fish) and the other is a
part of the dentary, a membraneous bone.
The modular nature and evolutionary plasticity of the
mammalian dentary bone has allowed for morphological
variation so that mammals have been able to exploit the
maximum range of dietary niches and the variation in
mechanical load of different foods. The different mechani-
cal loads acting on the dentary, arising as a consequence of
different feeding strategies, result in changes to the shape
and size of the angular and condylar processes evident
between species, even closely related ones. For example,
within Muridae,OldWorldratsandmice,herbivorousspe-
cies require strong jaw closure muscles to generate a lateral
force in the chewing action to process a diet high in tough
cellulose. This has resulted in an angular process, where the
relevant muscle attachment is larger than that of closely
related but omnivorous species whose diet is less cellulose-
rich (Michaux et al. 2007). Similarly, the giant anteater,
Myrmecophaga tridactyla,doesnotneedtogeneratemuch
force during jaw closure and, consequently, the coronoid
process is virtually absent and the non-articulating mandib-
ular processes are vestigial or lost. Furthermore, as the angle
of the jaw opening is only required to be minimal, the con-
dylar process is small and the glenoid fossa shallow (Naples,
1999). In striking contrast, the large gape and strong bite of
the hippopotamus has resulted in a large angular process,
to ensure a large surface area for muscle attachment and a
robust condylar process (Anthwal & Tucker, 2012).
Influence of secondary cartilage and
mechanical force
In the mammalian dentary, one or more of the proximal
processes (coronoid, angular, condylar) can be capped with
asecondarycartilage,thecondylarplusoneortwoothers.
These secondary cartilages, which undergo secondary ossifi-
cation, act in the growth and patterning of the embryonic
A
C
B
Fig. 6 The mammalian jaw articulation (A,C) MicroCT images of an
adult mouse. (A) Condylar head of the dentary bone fitting into the
glenoid fossa of the upper jaw. (B) Frontal section through an adult
mouse jaw joint. The disc is sandwiched between the glenoid fossa
(above) and condylar (below). (C) Dentary bone. Cr, coronoid process;
A, angular process; Co, Condylar process.
ªª 2012 The Authors
Journal of Anatomy ªª 2012 Anatomical Society
The mammalian middle ear and jaw, N. Anthwal et al. 153
mandible, in addition to the role of the condylar cartilage
in forming the articulation and disc.
The distribution of secondary cartilage on the proximal
processes of the dentary is species-specific, with the posi-
tion, size and persistence of such cartilages acting to shape
the relative size of the coronoid, angular process and den-
tary as a whole. For example, in humans the angular pro-
cess looks very similar to the mouse angular process during
early development but in humans this process is not capped
by secondary cartilages and fails to extend out, resulting in
formation of the curved human angle. In contrast, in the
mouse the angular process is capped by a robust secondary
cartilage that leads to growth of this process and a pro-
nounced angular process at birth (Anthwal & Tucker, 2012).
As the evolution of the mammalian jaw joint would not
have been possible without the initiation of a secondary
cartilage at the condylar process, it is important that we
understand how such cartilages are initiated and the mech-
anisms behind their induction.
Secondary cartilages are not found in amphibians but are
found during the development of birds at the 24 articula-
tion sites of membranous bones, such as the quadra-
tojugal quadrate joint of the chick mandible (Buxton et al.
2003). In addition, avian secondary cartilages are found at
the sites of muscle attachment, such as the point of inser-
tion of the mandibular adductor muscles on the lower jaw
in the duck (Solem et al. 2011). The pattern of secondary
cartilages in the avian jaw is species-specific, reflecting dif-
ferences in diet and mechanical strain on the jaw, this pat-
tern being controlled by the neural crest (Solem et al.
2011).
Much of the literature outlining the origin of secondary
cartilages has utilised the developing chick as a model. In
this system, quadratojugal-quadrate joint secondary carti-
lages develop from Runx2-positive cells of the periosteum
of the quadratojugal bone in response to mechanical stimu-
lation and initiation of the HMG box containing transcrip-
tion factor Sox9,aregulatorofTypeIIcollagen(Hall&
Herring, 1990; Zhao et al. 1997; Buxton et al. 2003; Archer
et al. 2006). However, the secondary cartilages of the mam-
mal dentary processes appear to have a different develop-
mental programme, with Sox9 acting alongside Runx2 to
initiate membranous ossification from the mandibular mes-
enchyme (Shibata et al. 2006). In addition, mouse secondary
cartilages are able to develop in the absence of mechanical
stimulation, as demonstrated by the culturing of dentary
explants in the absence of movement (Anthwal et al. 2008),
and by the presence of mandibular secondary cartilage in
knockout mice that lack muscle (Rot-Nikcevic et al. 2007).
Furthermore, experiments inourlabhavesuggestedthat
secondary cartilage develops as a sesamoid in explant cul-
tures which fail to produce bone, indicating that secondary
cartilage can develop regardless of membranous ossifica-
tion Anthwal et al. 2008; N. Anthwal, Y. Chai, A.S. Tucker,
unpublished data). Histological studies in rat also suggest
that the condylar cartilage develops as a sesamoid (Vinkka,
1982). Taken together, these data suggest that in contrast
to the situation in chick, the secondary cartilages of rodents
do not develop from the periosteum of membranous bone,
rather that secondary cartilages and membranous bone
develop from the same population of skeletoblasts. In the
mouse, secondary cartilagesaremalformedorlostinAlk2
mutants and after loss of transforming growth factor
beta (Tgfb)signalling(Dudasetal.2004; Oka et al. 2007;
Anthwal et al. 2008).
There is some debate as to whether reptiles are able to
form secondary cartilages. Rieppel suggests that reptiles can
do so during fracture repair (Rieppel, 1993). However, an
alternative study by Irwin was unable to detect secondary
cartilages in incisions made in the bone of 19 reptile speci-
mens, 17 lizards from three species and two snakes from
two species, suggesting that only birds and mammals are
capable of secondary cartilage induction (Irwin & Ferguson,
1986). The uncertain status of reptilian secondary cartilages
suggests the possibility that secondary cartilages have
evolved independently. This hypothesis is certainly sup-
ported by the differences in avian and mammalian second-
ary cartilage function and development. The term
‘secondary cartilage’ is a very broad one, including as it
does mechanically induced cartilages, cartilages that
develop due to fracture of membranous bones and carti-
lages that develop as part of the normal patterning of a
membranous bone (Beresford, 1981). It may be useful to
distinguish architectural secondary cartilages, which have a
role in the normal morphogenesis of a membranous bone
such as the condylar cartilage, and reactive secondary carti-
lages, which develop in reaction to an external force. In
keeping with a need to define more accurately secondary
cartilages, it has recently beenshownthatinavianembryos,
secondary cartilage that formsatarticulationsitesiscon-
trolled by different mechanisms than closely developing sec-
ondary cartilage that forms at the insertion of muscles
(enthesis) (Solem et al. 2011). Enthesis and articular carti-
lage both require mechanical force to form, but express a
different pattern of genes and respond differently to block
of ion channels. Thus secondary cartilages, although mor-
phologically similar, are formed by very different mecha-
nisms within and between species, making accurate
comparisons difficult.
Tissue interactions between the dentary and
upper jaw
The evolutionary elaboration of the dentary to form a con-
dylar process has also requiredtheadditionofanarticula-
tion site within the squamosal bone. This articulation site
takes the form of the glenoid fossa, a cavity within the
squamosal upon which the condylar head sits to form the
hinge of the jaw. Much like the specialisation of the den-
tary, the evolution of the glenoid fossa has required the
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Journal of Anatomy ªª 2012 Anatomical Society
The mammalian middle ear and jaw, N. Anthwal et al.154
utilisation of a membranous bone in a mobile joint. How-
ever, unlike the condylar process, no secondary cartilages
have formed. As with the rest of the jaw articulation, little
is known about the development of the glenoid fossa,
although one recent study has revealed that interaction
with the condylar is vital for its formation. Conditional
knockout mouse strategies were used to disrupt the devel-
opment of the condylar process: genetic ablation of the
condylar cartilage with Wnt1
Cre
;Sox9
flox flox
mutants, and
dislocation of the joint with K14
Cre
;catnb
f(ex3)
mutants
(Wang et al. 2011). In both cases the glenoid fossa was initi-
ated but later regressed, indicating that tissue interaction
between the condylar cartilage and squamosal are required
for the development of a glenoid fossa. The use of mice
with a mutant allele of the BMP antagonist Noggin, which
experience a rapid expansion of Meckel’s cartilage thus dis-
placing the condylar from the articulation with the cranial
base, enabled the sustained development of a glenoid
fossa, albeit with an non-functional joint (Wang et al.
2011). This study suggests that the squamosal is competent
to form a glenoid cavity in the presence of an articulating
element, which need not be the condylar portion of the
dentary. Intriguingly, the fossil record offers one example
of such a situation: Probainognathus, a late Jurassic
cynodont, possessed a jaw articulation formed between the
glenoid fossa of the squamosal and the surangular, an
intramembraneous element of the non-mammalian tetra-
pod mandible lost in modern mammals (reviewed Luo,
2011). In addition to signals from the condylar to the fossa,
there also appear to be signals from the fossa to the condy-
lar, resulting in generation ofadisc,whichfailstoformif
the condylar does not contact the fossa (Wang et al. 2011).
Signalling is therefore in both directions to allow coordi-
nated development of the upper and lower jaws.
Fate of Meckel’s cartilage in mammals
In birds and reptiles Meckel’s cartilage remains unossified,
with the exception of the retroarticular process, and per-
sists as a core providing flexible structural support for the
lower jaw bones that wrap around it (Fig. 5B). In mam-
mals such support in the adult is perhaps unnecessary, as
the single dentary forms the lower jaw, and as a conse-
quence much of Meckel’s cartilage does not persist into
adulthood.
The fate of the mammalian Meckel’s is complex and dif-
fers along its length, reflecting its different environment
and function. The most proximal (caudal) part, as has been
discussed, undergoes endochondrial ossification, and forms
the malleus and incus (Amin & Tucker, 2006). This region of
Meckel’s has been shown to be Type X collagen positive, a
marker for transformation to bone (Chung & Nishimura,
1999). The most distal (rostral) tips form the rostral process
that joins the two arms of Meckel’s cartilage at the symphy-
sis (Bhaskar et al. 1953). In humans, this part of Meckel’s
cartilage persists, forming small nodules on the dorsal sur-
face of the symphysis (Rodriguez-Vazquez et al. 1997). In
the rat, the hyaline cartilage at the rostal tip is replaced by
fibrocartilage at the time of weaning, as the animal moves
from sucking to mastication (Bhaskar et al. 1953). The
rostral cartilage is lost when Alk2 is conditionally knocked
out in the neural crest (using Wnt1 cre). This results in loss
of the symphysis and the mandible bones remain separate
(Dudas et al. 2004). Alk2 is a type I receptor for BMP signal-
ling, indicating the important role the Bmps play in the
development of the rostral part of Meckel’s cartilage.
Meckel’s cartilage in the mid portion (running from the
molar primordium to the rostral process) can directly
undergo ossification or be resorbed to be replaced by bone
(Richman & Diewert, 1988; Rodriguez-Vazquez et al. 1997;
Harada & Ishizeki, 1998). In explant culture, cells of Meckel’s
cartilage have been shown to be able to develop into
osteoblasts (Richman & Diewert, 1988). Resorption com-
mences with a breakdown of the perichondrium, followed
by invasion of vasculature and an infiltrate of TRAP-positive
osteoclasts chondroclasts, and macrophages that engulf
the chondrocytes (Harada & Ishizeki, 1998). Chondrocytes of
Meckel’s cartilage may regulate their own cell fate through
matrix remodelling and expression of matrix-metallo-pro-
teinases (MMPs) (Sakakura et al. 2007). MMPs are a family
of proteases that degrade protein components of the extra-
cellular matrix. In this way they may influence cellular
development by altering the composition of ECM compo-
nents such as growth factors and cytokines. MMPs are
highly expressed in rheumatoid arthritis, a pathological
example of the resorption of uncalcified matrix. A range of
MMPs are associated with the mid-rostral section of
Meckel’s cartilage and may contribute to resorption. Inter-
estingly, the specific pattern of MMPs appears unique to
Meckel’s cartilage and is different from those found in limb
cartilages undergoing endochondrial ossification (Sakakura
et al. 2007).
Despite this region of Meckel’s not functioning as an
adult structure, it plays an integral supporting role as a
scaffold for the mandible throughout embryonic develop-
ment with defects in Meckel’s causing malformations of the
developing mandible (Ito et al. 2002; Dudas et al. 2004). In
humans, Meckel’s cartilage acts as an initial attachment site
for the muscles of the mandible. Once these muscles
lose contact with Meckel’s and reach the developing
dentary, transformation of Meckel’s cartilage commences
(Wyganowska-Swiatkowska & Przystanska, 2011). Loss of
muscle attachment to Meckel’s may therefore be a possible
stimulus for a change of fate for Meckel’s cartilage.
Breaking the connection between the ear
and jaw
Akeystepintheformationofthedenitivemammalian
middle ear (DMME) was the breakdown of Meckel’s carti-
ªª 2012 The Authors
Journal of Anatomy ªª 2012 Anatomical Society
The mammalian middle ear and jaw, N. Anthwal et al. 155
lage between the forming dentary and malleus. From the
fossil record it is clear that the articular and quadrate were
already playing a part in hearing and had lined up with the
stapes in the middle ear before they became physically
separated from the jaw. Breakdown of Meckel’s cartilage is
thus the final step in the move towards the definitive
mammalian ear. Although the mechanisms of removal are
unclear, the consequence is to free the first two ossicles of
the middle ear from the rest of the cartilage, in this way
removing the connection between the jaw and middle ear
and functionally separating the feeding and hearing
apparatuses. This is an adaptation seen in all living adult
mammals today.
The timing of the break variesbetweenspecies.Ashas
already been mentioned, this occurs relatively late in marsu-
pials, at around P20, but a late break is also observed in the
placental tree shrew (Tupaia), where Meckel’s remains con-
necting the ear to the jaw until around P14, and is thought
to function as a skeletal support (Zeller, 1987). In humans,
Meckel’s cartilage breaks down by the 8th month of gesta-
tion (Cheynet et al. 2003). In clinical cases where the tempo-
romandibular joint does not develop, Meckel’s remains
continuous (Herring, 1993). The stimulus for breakdown of
Meckel’s may therefore be linked to development of a func-
tional TMJ.
During development, the stretch of Meckel’s cartilage
from the molar primordium to the malleus undergoes an
unusual transformation to form a fibrous ligamentous
structure (Harada & Ishizeki, 1998), which develops into the
sphenomandibular and anterior malleolar ligaments
(Ogutcen-Toller, 1995; Cheynet et al. 2003). The spheno-
mandibular (also known as the malleomandibular) is
involved in TMJ movement by limiting the distension of the
mandible and preventing dislocation and forms between
the sphenoid bone and dentary. The connected anterior
malleolar ligament attaches to themalleusandanteriorwall
of the tympanic cavity and acts to stabilise the mandible.
The transformation process has been studied in the
mouse and rat. By postnatal day 3 in mice this portion of
Meckel’s cartilage no longer stains with Alcian Blue, a dye
for cartilage-associated matrixproteoglycans(Fig.7AC).In
histological section the cartilage can be seen to thin in this
region, the rounded cartilage cells disappearing, to be
replaced by elongated fibroblastic cells (Fig. 7D–F). The
transformation process starts close to the malleus and then
spreads out in a wave towards the dentary. No invasion of
vasculature, macrophages or osteoclasts was observed in
this part of Meckel’s (Harada & Ishizeki, 1998). Organ cul-
ture of this region of Meckel’scartilageintheratshows
that isolated cartilage that has been stripped of the perioc-
hondrium differentiates into cells of fibroblast morphology,
which do not express cartilage specific proteoglycans typical
of chondrocytes (Richman & Diewert, 1988). It is the carti-
lage cells themselves, therefore, rather than the perichon-
drium, that undergo this transformation. Cells in this region
do not proliferate to give rise to fibroblasts, suggesting the
potential to alter their cell fate from chondrocytes and
transform directly into fibroblasts themselves. Cell death is
not observed within this mid region although it is seen in
the perichondrium of the mandibular and auricular regions
(Trichilis & Wroblewski, 1997;Harada&Ishizeki,1998).
Meckel’s cartilage has beensuccessfullyculturedin vitro
and has proved a valuable tool for assessing the compe-
tence of Meckel’s to undergo different fates and look at
the role of growth factors (Richman & Diewert, 1988;
Harada & Ishizeki, 1998; Ishizeki et al. 2001). When Meckel’s
cartilage from rat embryos at embryonic day (E)17 was
cultured in ocular grafts, the different regions of Meckel’s
Fig. 7 Breakdown of Meckel’s cartilage (A–C) Skeletal preps of the mouse malleus and Meckel’s cartilage. Red – bone stained by Alizarin Red.
Blue – cartilage stained by Alcian Blue. (A) P0. (B) P1. (C) P3. (D–F) Histology sagittal sections through the transforming Meckel’s cartilage. (D) P0.
(E) P1. (F) P2. Arrows points to region where breakdown initiates. Me, Meckel’s cartilage; M, malleus.
ªª 2012 The Authors
Journal of Anatomy ªª 2012 Anatomical Society
The mammalian middle ear and jaw, N. Anthwal et al.156
continued to develop into their normal fates (bone, liga-
ment, etc.) (Richman & Diewert, 1988). This suggests rat
chondrocytes of Meckel’s cartilage from E17 onwards are
specified to follow their terminal cell fates. However, when
mouse E17 Meckel’s cartilage wasdissectedandculturedin
dishes it was found to ossify (Ishizeki et al. 2001). The
default state for this region of Meckel’s therefore appears
to be to undergo ossification. A similar result was found
when Meckel’s chondrocytes from mouse E17 embryos were
grown in tissue culture, the cells expressing Type X collagen
and osteocalcin and forming nodules with calcification of
the matrix, indicating a transformation to osteogenic cells
(Ishizeki et al. 1997). Clinical cases where Meckel’s fails to
breakdown and ossifies have been reported in human
fetuses, but these are very rare (Keith, 1910).
That Meckel’s cartilage forms bone when isolated during
development fits well with the finding of an ossified Mec-
kel’s in the fossil record. If the default state of Meckel’s car-
tilage is to ossify, then an important step in mammalian
evolution would have been the prevention of ossification in
this region. Studies have implicated two signalling path-
ways in this step, epidermal growth factor (EGF) and trans-
forming growth factor beta (TGFb).
For example, ossification of Meckel’s cartilage, as indi-
cated by staining for Alizarin Red, could be prevented in
Meckel’s cartilage cultures by the addition of epidermal
growth factor (EGF). Instead of formation of a mineralized
matrix, the cells transformed toaligamentousfate,asthey
would have done in the embryo (Ishizeki et al. 2001). Addi-
tion of EGF caused cells to proliferate, downregulate carti-
lage type proteoglycans and adopt fibroblastic
morphologies that expressed type 1 collagen. Interestingly
these alterations in response to EGF were uniform through-
out Meckel’s cartilage, suggesting that chondrocytes of
Meckel’s cartilage have homogeneous potential to respond
to EGF (Ishizeki et al. 2001).
To investigate the effect of EGF in vivo,EGFwasinjected
into newborn mice. This resulted in an accelerated disappear-
ance of Meckel’s cartilage, indicated by a more rapid loss of
Alcian Blue staining between the dentary and the ossicles.
Taken together, this study implicates EGF as potential
inducer of chondrocyte to fibroblast transformation, sug-
gesting EGF may control the boundaries and formation of
the sphenomandibular ligament in vivo.
In the TGFbr2 knockout, in addition to a number of
defects associated with the dentary, Meckel’s cartilage
ossifies at birth (Oka et al. 2007; Anthwal et al. 2008).
This ossification occurs in the mid region, which would
usually be resorbed and transformed into the spheno-
mandibular ligament. In Tgfbr2 mutants, Dlx 5 expres-
sion is upregulated (Oka et al. 2008) and, intriguingly,
an ossified Meckel’s is also observed in Dlx5
))
mutants
and Dlx1
))
;Dlx5
+
1double mutants (Depew et al.
2005). Lack of Tgfbsignalling causes Indian hedgehog
(Ihh), a gene expressed in differentiating but not imma-
ture chondrocytes, to have an expanded expression
domain, implying that loss of Tgfbcauses accelerated
differentiation of chondrocytes (Oka et al. 2007). In nor-
mal mammalian development, the mid region of Mec-
kel’s would receive a signal to transform to a
ligamentous fate. If this signal is not received, as in the
case of the cultures of Meckel’s cartilage, these cells will
follow a bone differentiation pathway, or if these cells
start on an ossification pathway before they receive the
signal, as in the case of Tgfbr2 mutants, then an ossified
connection is created between the mandible and middle
ear. Therefore Tgfbsignalling may indirectly control the
fate of the mid region by slowing down chondrocyte
differentiation to maintainresponsivenesstosignalling
factors that initiate the transformation of this region.
Most likely, Tgfbsignalling will act in concert with other
growth factors such as EGF to control developmental
timing of proliferation, differentiation and therefore the
fate of chondrocytes in Meckel’s cartilage. The tempo-
rary presence of Meckel’s cartilage during embryonic
and early postnatal stages in living mammals may impli-
cate the ossified Meckel’s cartilage (OMC) in ancestral
mammals, an example of paedomorphosis, the retention
of an embryonic structure in the mature adult (Ji et al.
2009; Luo, 2011). Paedomorphosis is a result of develop-
mental heterochrony, that is, the shift in timing of a
particular genetic pathway. Therefore the timing of Tgfb
signalling, EGF signalling, chondrocyte differentiation
and ossification could perhaps have been a determining
factor for the fate of the mid portion of Meckel’s carti-
lage and in this way determined whether it was
retained as an ossified adult structure or transformed
into a ligament.
Conclusion
In conclusion, the evolution of the mammalian middle
ear and jaw joint were pivotal steps in the evolution of
mammals. It is also a great example of how classical
comparative anatomy, paleontology and developmental
biology have come together to piece together how this
remarkable transformation of jaw joint to ear ossicles
was able to come about. The homologies of the mal-
leus, incus and stapes to the articular, quadrate and col-
umella, and tympanic ring and gonial to the angular
and prearticular suggested by comparative anatomy
175 years ago have been recently confirmed by molecu-
lar and developmental biology. The recent discovery of
new mammaliform fossils has allowed careful documen-
tation of the shift from primary to secondary jaw articu-
lation, creating an opportunity to follow the
transformation of the post-dentary skeletal elements.
This fossil data has been complemented by the study of
marsupial development, providing insight into the
changing role of the malleus and incus, and the rela-
ªª 2012 The Authors
Journal of Anatomy ªª 2012 Anatomical Society
The mammalian middle ear and jaw, N. Anthwal et al. 157
tionship of the primary and secondary jaw joints. We
now have a number of unanswered questions. What are
the signalling molecules involved in the interactions
between the condylar process and the glenoid fossa that
create the novel mammalian jaw joint? What are the
mechanisms that lead to transformation of Meckel’s car-
tilage into a ligament allowing isolation of the ear from
the jaw? What controls the distribution of secondary car-
tilages? What controls the timing of differentiation and
cessation of growth of the ossicles relative to the jaw?
With the new tools available to us we hope to be able
to address some of these questions and provide insights
into the mechanisms that lie behind evolution.
Acknowledgements
Thanks to Robert Asher and Zhe-Xi Luo for discussions on the
evolution of the ear. Thanks to Kathleen Smith for the image of
the Monodelphis neonate. Thanks to Hannah Thompson for her
comparative diagram of the middle ear (Fig. 4). Leena Joshi is
supported by Deafness Research UK. Abigail Tucker is supported
by the Medical Research Council (MRC). The authors declare no
conflict of interest.
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The edentulous giant anteater (Myrmecophaga tridactyla) ingests food using a slender, elongated sticky tongue which can project to a distance greater than the cranial length. A large and elongated hyoid apparatus, including a long stylohyal, epihyal, reduced ceratohyal and fused basihyal-thyrohyal fused to a partially ossified thyroid cartilage, supports the tongue. The fusion pattern and relative hyoid element sizes in adult Myrmecophaga differ from those in other xenarthran anteaters, tree and ground sloths, and armadillos. The hyoid bones have synovial joints with articular surfaces permitting great freedom of movement. A unique hyoid muscle arrangement enables Myrmecophaga to project the tongue with great speed and precise positional control. This muscle arrangement combined with an elongated secondary palate, accommodates the retracted tongue within the oropharynx without compromising the animal's ability to breathe. Maximum gape is reached at a few degrees of mandibular depression, but the oral opening is increased to 2 cm by the extreme length of the anterior facial region. Gape is further increased by medial rotation and depression of the unfused mandibular rami at the mental symphysis. This movement, even without mandibular depression, permits protraction and retraction of the elongated tongue. Mandibular rotation in lieu of depression and elevation simplifies jaw movements made by a smaller uniquely modified muscle mass over shorter distances, therefore increasing the speed with which anteaters can ingest food, and complements the extremely rapid tongue protrusion-retraction cycle.
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