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Scientists have long been searching for fossils of distant vertebrate ancestors. In the 1990s, mysterious fishlike forms—now known as yunnanozoans—were discovered at a 520-million-year-old Cambrian fossil site in the Yunnan province of China (1–3). More fishlike forms (e.g., Haikouichthys and Myllokunmingia) were reported from the same locality shortly thereafter (4, 5), while the 508-million-year-old Burgess Shale in the Canadian Rockies yielded Metaspriggina (6). Having eyes and a brain at the front end of an otherwise wormlike soft body, these animals appear to have branched off the phylogenetic tree before the last common ancestor of all living vertebrates. However, there is ongoing controversy about precisely how close to vertebrates these Cambrian forms were. On page 218 of this issue, Tian et al. (7) present compelling evidence in yunnanozoans for an unmistakable vertebrate trait—a pharyngeal skeleton made of cellular cartilage.
pramolecular network. This component com-
prises a ureidopyrimidinone (UPy) supramo-
lecular motif that forms long fiber bundles
(8). Although the UPy motif also interacts
with the surfactant, the assembled UPy fiber
bundles are not evidently disturbed by the
presence of surfactant. By this approach, the
system of BTA-EG4 and surfactant, at concen-
trations that previously formed a sol consist-
ing of spherical assemblies, can instead form
a gel by adding a high concentration of UPy
fibrillar structures. Dilution from this ini-
tial point surpasses the gelation capacity of
the UPy network while not yet reaching the
point of inducing BTA-EG4 filament forma-
tion, yielding a sol. Continued dilution acti-
vates BTA-EG4 filament formation, which in
combination with the remaining UPy fiber
bundles restores a gel state comprising two
orthogonal networks of supramolecular poly-
mers: the BTA-EG4 and UPy networks. Upon
further dilution, the system transitions back
to a sol once again.
The tunable nature of molecular-scale self-
assembly in these materials offers simple
synthetic analogues of more complex phe-
nomena observed in nature. For example,
membraneless organelles—distinct compart-
ments within a cell that are not enclosed by
a traditional lipid membrane—are thought
to arise from liquid-liquid phase separation
because of concentration gradients of as-
sociating multicomponent systems forming
these assemblies in a water environment (9).
The roles of membraneless organelles in bio-
logical signaling during both normal and dis-
eased states are increasingly appreciated (10).
The behavior of the simple systems described
by Su et al. is therefore reminiscent of more
complex self-assembly phenomena in biol-
ogy, illuminating the importance of subtle
thermodynamic driving forces that give rise
to concentration-dependent phase separa-
tion. This new paradigm in self-assembled
materials consisting of highly adaptive and
dilution-triggered hydrogels may further-
more lead to the design of stimuli-responsive
material platforms for in situ modulation of
function in therapeutic biomedicine. j
1. M. A. Stuart et al ., Nat. Mater.9, 101 (2010).
2 . L. S u et al., Science 377, 213 (2022).
3. T. Aida, E. W. Meije r, S. I. Stup p, Science 335, 813 (2012).
4. M. J. Rose n, J. T. Kunjap pu, Surfactants and Interfacial
Phenomena (Wi ley, e d. 4, 2 012 ).
5. K. L. M orris et al ., Nat. Commun.4, 1480 (2013).
6. W. M. Jacobs , D. Frenkel , Biophys. J.112, 683 (2017).
7. C. M. Leende rs et a l., Chem. Commun. 49, 1963 (2013).
8. S. I. S. He ndriks e et a l., Chem. Commun.53, 2279 (2017).
9. J. A. Riba ck et al., Nature 581, 209 (2020).
10. Y. Shin, C. P. Brangwynne, Science 357, eaaf4382 (2017).
M.J.W. acknowledges funding from the National Institutes of
Health (R35GM137987) and the National Science Foundation
(BMAT, 1944875).
By Tetsuto Miyashita
Scientists have long been searching
for fossils of distant vertebrate an-
cestors. In the 1990s, mysterious
fishlike forms—now known as yun-
nanozoans—were discovered at a
520-million-year-old Cambrian fossil
site in the Yunnan province of China (13).
More fishlike forms (e.g., Haikouichthys and
Myllokunmingia) were reported from the
same locality shortly thereafter (4, 5), while
the 508-million-year-old Burgess Shale in the
Canadian Rockies yielded Metaspriggina (6).
Having eyes and a b rain at the front end of an
otherwise wormlike soft body, these animals
appear to have branched off the phylogenetic
tree before the last common ancestor of all
living vertebrates. However, there is on going
controversy about precisely how close to
vertebrates these Cambrian forms were. On
page 218 of this issue, Tian et al. (7) present
compelling evidence in yunnanozoans for an
unmistakable vertebrate trait—a pharyngeal
skeleton made of cellular cartilage.
Interpreting organic stains on a shale slab
is both a science and an art. Wielding scan-
ning electron microscopy and computed mi-
crotomography scans to yield unprecedented
details, Tian et al. reveal cellular and subcel-
lular structures of the skeletal bars that best
compare to cartilaginous gill arches of mod-
ern vertebrates. These bars in yunnanozoans
are patterned in a s eries, ea ch associ ated with
gill filaments and connected by horizontal
rods. The morphology closely approximates
various predictions for vertebrate ancestors.
Of all the internal structures of the earli-
est vertebrates, pharyngeal skeletons perhaps
stand the best chance for fossilization given
their robustness. Nonetheless, the complex
evolutionary history of the pharynx has
Arch”-etyping vertebrates
Cellular details of gill arches in Cambrian fossils reignite
a centuries-old debate
Pharyngeal skeleton Gill laments Myomeres
Of gills and jaws
Cambrian vertebrates each evolved distinct pharyngeal anatomy with a series of gill-supporting skeletons.
The yunnanozoan has a cartilaginous basket and the Haikouichthys has unjoined bars, whereas the
Metaspriggina has upper and lower rods. However, it remains an open question whether their gill anatomies
represent any evolutionary link to the jaws of modern vertebrates.
154 8 JULY 2022 • VOL 377 ISSUE 6602
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strained attempts to interpret fossil imprints.
Pharyngeal slits and skeletons long precede
the origins of vertebrates, and cellular car-
tilage has been found in the lips of a devel-
oping invertebrate chordate (8). Vertebrates
develop the entire pharyngeal skeleton from
cellular cartilage in the embryonic pharyn-
geal arches. This cartilage originates in the
vertebrate-specific cell lineage called the neu-
ral crest. To complicate matters further, the
pharynx is regionally and phylogenetically
differentiated among vertebrates. Depending
on whether similarities or differences are
emphasized, the pharyngeal arch I in which
jaws develop, that is, the mandibular arch,
may (911) or may not (1214) share an evolu-
tionary origin with gill-supporting skeletons.
New information from yunnanozoans pre-
sents an opportunity to clarify these issues.
Tian et al. avoided jumping to conclusions,
as they did not explicitly identify which gill
bar in a yunnanozoan corresponds to which
arch in a modern vertebrate. But they did
signal their favored interpretation that yun-
nanozoans, with each gill bar identical to the
next, represent the ancestral vertebrate con-
dition. This view is in line with the belief that
all pharyngeal arches originally supported
gills and that one of them evolved into a jaw
(911). At face value, yunnanozoans could
serve as long-awaited evidence for the gill-
arch hypothesis of jaw origins.
However, this jaw-origin narrative relies
solely on how one chooses to identify the gill
bars of yunnanozoans—that is, whether the
first gill bar in yunnanozoans corresponds
to the mandibular arch in jawed vertebrates.
Historically, one or more additional arches
were postulated in front of the mandibu-
lar arch for vertebrate ancestors (11). Other
views posit no such extra arches and consider
the mandibular arch as distinct from the gill
arches (1214). Yunnanozoan morphology
excludes none of these ideas. Their first gill
bar could be the elusive arch that was later
lost in vertebrates, or, conversely, the man-
dibular region might not have formed a full
skeletal arch. Consistent with the latter sce-
nario, the snout and lips either appear di-
minutive or are absent in yunnanozoans and
other Cambrian forms (57). Specifically, one
C-shaped oral structure, as identified by Tian
et al., may represent what might be a slim
mandibular arch of yunnanozoans. If this is
true, then a prominent snout and lips, which
arise from the neural crest, are a later innova-
tion of the living vertebrate group.
To discriminate between different hypoth-
eses, unequivocal correlates of arch identities
are needed. A mandibular arch is not defined
by being the most anterior pharyngeal arch.
Rather, its identity is predicated on the pres-
ence of a specific stream of neural crest cells,
a fifth cranial nerve, and specialized mouth
structures for pumping water and feeding.
Without these markers, and with variations
observed among different vertebrate lineages,
overall positions of the gills help little to de-
termine arch homology in yunnanozoans.
Tian et al. offer an emerging scope of
diversity in pharyngeal anatomy of early
vertebrates (see the figure). Among other
Cambrian fishlike forms, Haikouichthys
seems to have skeletal rods that support
the gills, whereas only the gill pouches
are described for Myllokunmingia (4).
Metaspriggina has skeletal bars segmented
into upper and lower halves (6). Hagfish and
lampreys evolved from the common ances-
tor with a cartilaginous basket around the
gill pouches and a specialized oral skeleton
(15). Similar pharyngeal skeletons also occur
in successive out-groups of jawed vertebrates
(12). And jawed vertebrates have a series of
jointed skeletal arches, the first of which dif-
ferentiate as jaws. These different patterns
are as anatomically disconnected from each
other as they are phylogenetically distant.
Given such a complex distribution of char-
acters, it seems premature to assume any sin-
gle form as the ancestral phenotype on a lin-
ear path toward modern vertebrates. In the
phylogenetic analysis by Tian et al., yunnano-
zoans are an out-group to all other vertebrate
branches. This suggests differential evolution
of pharyngeal patterning among early ver-
tebrate lineages. By the time yunnanozoans
were sloshing about in the Cambrian sea,
other primitive fishes had evolved to slurp
food differently with their uniquely derived
pharyngeal anatomy. Although evolutionary
biologists have been busy chasing the mythi-
cal ancestor that explains everything about
the vertebrate body plan, perhaps the oppo-
site is a sensible approach. In other words,
the meandering journey toward modern
vertebrates may be best understood by popu-
lating the family tree with divergent and dis-
continuous anatomical forms, guided by phy-
logenetic inference rather than by theory. j
1. J.-Y. Chen et al ., Nature 377, 720 (1995).
2. J.-Y. Chen et a l., Nature 402, 518 (1999).
3. D. Shu et al ., Science 299, 1380 (2003).
4. D.-G. Shu et a l., Nature 402, 42 (1999).
5. D.-G. Shu et a l., Nature 421, 526 (2003).
6. S. Co nway Mor ris , J.-B . Ca ron, Nature 512, 419 (2014).
7. Q. Tian et a l., Science 377, 218 (2022).
8. D. Jandz ik et a l., Nature 518, 534 (2015).
9. J. A. Gillis et al. , Nat. C omm un. 4, 1436 (2013).
10. C. Hirschberger et a l., Mol. Biol. Evol. 38, 418 7 (2 021 ).
1 1. J. Mallatt, Zoolog. J. Lin n. Soc. 117, 329 (2008).
1 2. P. Janvie r, Early Vertebrates (Oxford Monographs on
Geology and Geophysics, Clarendon Press, 1996).
13. S. Kuratani, Evol . Dev. 14, 76 (2012).
14. T. Miyashita, Bio l. Rev. Cam b. Ph ilos . Soc . 91, 611 (2016).
15. T. Miyashita, Can. J. Zool. 98, 850 (2020).
By Rohini Kuner1 and Thomas Kuner2
The perception of physical pain is sub-
ject to variation depending on the
context and which other sensory in-
puts are being received, including
sound. The emerging field of music
therapy (1)—which is applied to con-
trol postoperative, pediatric, postpartum,
and cancer pain and is being increasingly
tested in chronic pain disorders—capital-
izes on the interactions between sound and
pain perception to attenuate pain. Given
that music and natural sounds can posi-
tively affect mood, relieve stress, and relax
the body, it is not unreasonable to think
that these factors underlie pain relief. On
page 198 of this issue, Zhou et al. (2) demon-
strate that pain relief by sound is not purely
attributable to stress reduction and distrac-
tion. They interrogate neural circuits to un-
ravel a specific pathway for sound-induced
analgesia in the brains of mice.
Using rodents to study how music and
sound are related to pain presents major
challenges, not least because it is unknown
how animals perceive music. Zhou et al. car-
ried out behavioral tests addressing pain
sensitivity and found that mice did not show
differential responses to melodic classical
music (consonant sounds), dissonant mu-
sic, or white noise. Notably, they found that
the decisive factor in eliciting pain relief is
a 5-dB increase in sound intensity in any of
these three types of sound relative to ambi-
ent sound levels, whereas 10-, 15-, or 20-dB
increases were ineffective. In mouse mod-
els, a 5-dB increase in sound intensity led
to inhibition of both sensory-discriminative
aspects of pain, such as evoked responses
aiding escape from noxious stimuli (nocicep-
tion), and affective behaviors that are linked
to suffering and negative emotions associated
with acute and chronic pain. Therapeutically
relevant findings were that repetitive ap-
plication of 5-dB sound over ambient levels
out pain
A circuit for sound-induced
analgesia has been found in
the mouse brain
1Institute of Pharmacology, Heidelberg University,
Heidelberg, Germany. 2Department of Functional
Neuroanatomy, Institute for Anatomy and Cell Biology,
Heidelberg University, Heidelberg, Germany.
Canadian Museum of Nature, Ottawa, Ontario K1P 6P4,
Canada. Email:
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Science (ISSN 1095-9203) is published by the American Association for the Advancement of Science. 1200 New York Avenue NW,
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Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim
to original U.S. Government Works
“Arch”-etyping vertebrates
Tetsuto Miyashita
Science, 377 (6602), • DOI: 10.1126/science.adc9198
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Tian et al. (Reports, 8 July 2022, p. 218) claim that Cambrian yunnanozoan animals are stem vertebrates, based partly on their observation at the nanometer scale of microfibrillar tissue located in the branchial arches. They interpret this to represent cellular cartilage with an extracellular matrix of microfibrils. Instead, we argue that the 'microfibrils' are more likely modern organic contamination.
Full-text available
The origin of the jaw is a long-standing problem in vertebrate evolutionary biology. Classical hypotheses of serial homology propose that the upper and lower jaw evolved through modifications of dorsal and ventral gill arch skeletal elements, respectively. If the jaw and gill arches are derived members of a primitive branchial series, we predict that they would share common developmental patterning mechanisms. Using candidate and RNAseq/differential gene expression analyses, we find broad conservation of dorsoventral patterning mechanisms within the developing mandibular, hyoid and gill arches of a cartilaginous fish, the skate (Leucoraja erinacea). Shared features include expression of genes encoding members of the ventralising BMP and endothelin signalling pathways and their effectors, the joint markers nkx3.2 and gdf5 and pro-chondrogenic transcription factor barx1, and the dorsal territory marker pou3f3. Additionally, we find that mesenchymal expression of eya1/six1 is an ancestral feature of the mandibular arch of jawed vertebrates, while differences in notch signalling distinguish the mandibular and gill arches in skate. Comparative transcriptomic analyses of mandibular and gill arch tissues reveal additional genes differentially expressed along the dorsoventral axis of the pharyngeal arches, including scamp5 as a novel marker of the dorsal mandibular arch, as well as distinct transcriptional features of mandibular and gill arch muscle progenitors and developing gill buds. Taken together, our findings reveal conserved patterning mechanisms in the pharyngeal arches of jawed vertebrates, consistent with serial homology of their skeletal derivatives, as well as unique transcriptional features that may underpin distinct jaw and gill arch morphologies.
Full-text available
Hagfishes and lampreys comprise cyclostomes, the earliest branching and sole surviving clade of the once diverse assemblage of jawless crown-group vertebrates. Lacking mineralized skeletons, both of the crown cyclostome lineages have notoriously poor fossil record. Particularly in the hagfish total group, †Myxinikela siroka Bardack, 1991 from the Late Carboniferous estuarine system of Illinois (USA) represents the only definitive stem taxon. Previously known from a single specimen, Myxinikela has been reconstructed as a short-bodied form with pigmented eyes but otherwise difficult to distinguish from the living counterpart. With a new, second specimen of Myxinikela reported here, I reevaluate the soft tissue anatomy and formulate diagnosis for the taxon. Myxinikela has a number of general features of cyclostomes, including cartilaginous branchial baskets, separation between the esophageal and the branchial passages, and a well-differentiated midline finfold. In effect, these features give more lamprey-like appearance to this stem hagfish than previously assumed. Myxinikela still has many traits that set modern hagfishes apart from other vertebrates (e.g., nasohypophyseal aperture, large velar cavity, and cardinal heart) and some intermediate conditions of modern hagfishes (e.g., incipient posterior displacement of branchial region). Thus, Myxinikela provides an important calibration point with which to date origins of these characters.
Full-text available
The evolutionary origin of the vertebrate jaw persists as a deeply puzzling mystery. More than 99% of living vertebrates have jaws, but the evolutionary sequence that ultimately gave rise to this highly successful innovation remains controversial. A synthesis of recent fossil and embryological findings offers a novel solution to this enduring puzzle. The Mandibular Confinement Hypothesis proposes that the jaw evolved via spatial confinement of the mandibular arch (the most anterior pharyngeal arch within which the jaw arose). Fossil and anatomical evidence reveals: (i) the mandibular region was initially extensive and distinct among the pharyngeal arches; and (ii) with spatial confinement, the mandibular arch acquired a common pharyngeal pattern only at the origin of the jaw. The confinement occurred via a shift of a domain boundary that restricted the space the mesenchymal cells of the mandibular arch could occupy. As the surrounding domains replaced mandibular structures at the periphery, this shift allowed neural crest cells and mesodermal mesenchyme of the mandibular arch to acquire patterning programs that operate in the more posterior arches. The mesenchymal population within the mandibular arch was therefore no longer required to differentiate into specialized feeding and ventilation structures, and was remodelled into a jaw. Embryological evidence corroborates that the mandibular arch must be spatially confined for a jaw to develop. This new interpretation suggests neural crest as a key facilitator in correlating elements of the classically recognized vertebrate head 'segmentation'. © 2015 Cambridge Philosophical Society.
Full-text available
Gegenbaur's classical hypothesis of jaw-gill arch serial homology is widely cited, but remains unsupported by either palaeontological evidence (for example, a series of fossils reflecting the stepwise transformation of a gill arch into a jaw) or developmental genetic data (for example, shared molecular mechanisms underlying segment identity in the mandibular, hyoid and gill arch endoskeletons). Here we show that nested expression of Dlx genes-the 'Dlx code' that specifies upper and lower jaw identity in mammals and teleosts-is a primitive feature of the mandibular, hyoid and gill arches of jawed vertebrates. Using fate-mapping techniques, we demonstrate that the principal dorsal and ventral endoskeletal segments of the jaw, hyoid and gill arches of the skate Leucoraja erinacea derive from molecularly equivalent mesenchymal domains of combinatorial Dlx gene expression. Our data suggest that vertebrate jaw, hyoid and gill arch cartilages are serially homologous, and were primitively patterned dorsoventrally by a common Dlx blueprint.
Full-text available
THE first chordate recorded from the Early Cambrian is the ceph-alochordate Yunnanozoon lividum from the 525 million-year-old Chengjiang fauna. Chordate features of Yunnanozoon are a noto-chord and an expanded filter-feeding pharynx with an endostyle. Segmented musculature and metameric branchial arches are shared with cephalochordates and craniates. Metameric gonads and an anteriorly extended notochord indicate cephalochordate affinities. Yunnanozoon expands the range of cephalochordate morphology known from the younger Pikaia gracilens and crown group forms such as amphioxus. Our identification predicts that other chordate clades (tunicates and craniates) had evolved by the Late Atdabanian, in the main burst of the Cambrian Explosion.
Pharyngeal arches are a key innovation that likely contributed to the evolution of the jaws and braincase of vertebrates. It has long been hypothesized that the pharyngeal (branchial) arch evolved from an unjointed cartilaginous rod in vertebrate ancestors such as that in the nonvertebrate chordate amphioxus, but whether such ancestral anatomy existed remains unknown. The pharyngeal skeleton of controversial Cambrian animals called yunnanozoans may contain the oldest fossil evidence constraining the early evolution of the arches, yet its correlation with that of vertebrates is still disputed. By examining additional specimens in previously unexplored techniques (for example, x-ray microtomography, scanning and transmission electron microscopy, and energy dispersive spectrometry element mapping), we found evidence that yunnanozoan branchial arches consist of cellular cartilage with an extracellular matrix dominated by microfibrils, a feature hitherto considered specific to vertebrates. Our phylogenetic analysis provides further support that yunnanozoans are stem vertebrates.
A defining feature of vertebrates (craniates) is a pronounced head that is supported and protected by a robust cellular endoskeleton. In the first vertebrates, this skeleton probably consisted of collagenous cellular cartilage, which forms the embryonic skeleton of all vertebrates and the adult skeleton of modern jawless and cartilaginous fish. In the head, most cellular cartilage is derived from a migratory cell population called the neural crest, which arises from the edges of the central nervous system. Because collagenous cellular cartilage and neural crest cells have not been described in invertebrates, the appearance of cellular cartilage derived from neural crest cells is considered a turning point in vertebrate evolution. Here we show that a tissue with many of the defining features of vertebrate cellular cartilage transiently forms in the larvae of the invertebrate chordate Branchiostoma floridae (Florida amphioxus). We also present evidence that during evolution, a key regulator of vertebrate cartilage development, SoxE, gained new cis-regulatory sequences that subsequently directed its novel expression in neural crest cells. Together, these results suggest that the origin of the vertebrate head skeleton did not depend on the evolution of a new skeletal tissue, as is commonly thought, but on the spread of this tissue throughout the head. We further propose that the evolution of cis-regulatory elements near an ancient regulator of cartilage differentiation was a major factor in the evolution of the vertebrate head skeleton.
Knowledge of the early evolution of fish largely depends on soft-bodied material from the Lower (Series 2) Cambrian period of South China. Owing to the rarity of some of these forms and a general lack of comparative material from other deposits, interpretations of various features remain controversial, as do their wider relationships amongst post-Cambrian early un-skeletonized jawless vertebrates. Here we redescribe Metaspriggina on the basis of new material from the Burgess Shale and exceptionally preserved material collected near Marble Canyon, British Columbia, and three other Cambrian Burgess Shale-type deposits from Laurentia. This primitive fish displays unambiguous vertebrate features: a notochord, a pair of prominent camera-type eyes, paired nasal sacs, possible cranium and arcualia, W-shaped myomeres, and a post-anal tail. A striking feature is the branchial area with an array of bipartite bars. Apart from the anterior-most bar, which appears to be slightly thicker, each is associated with externally located gills, possibly housed in pouches. Phylogenetic analysis places Metaspriggina as a basal vertebrate, apparently close to the Chengjiang taxa Haikouichthys and Myllokunmingia, demonstrating also that this primitive group of fish was cosmopolitan during Lower-Middle Cambrian times (Series 2-3). However, the arrangement of the branchial region in Metaspriggina has wider implications for reconstructing the morphology of the primitive vertebrate. Each bipartite bar is identified as being respectively equivalent to an epibranchial and ceratobranchial. This configuration suggests that a bipartite arrangement is primitive and reinforces the view that the branchial basket of lampreys is probably derived. Other features of Metaspriggina, including the external position of the gills and possible absence of a gill opposite the more robust anterior-most bar, are characteristic of gnathostomes and so may be primitive within vertebrates.
Since the identification of the Lower Cambrian Yunnanozoon as a chordate in 1995 (ref. 1), large numbers of complete specimens of soft-bodied chordates from the Lower Cambrian Maotianshan Shale in central Yunnan (southern China) have been recovered. Here we describe a recently discovered craniate-like chordate, Haikouella lanceolata, from 305 fossil specimens in Haikou near Kunming. This 530 million-year-old (Myr) fish-like animal resembles the contemporaneous Yunnanozoon from the Chengjiang fauna (about 35km southeast of Haikou) in several anatomic features. But Haikouella also has several additional anatomic features: a heart, ventral and dorsal aorta, an anterior branchial arterial, gill filaments, a caudal projection, a neural cord with a relatively large brain, a head with possible lateral eyes, and a ventrally situated buccal cavity with short tentacles. These findings indicate that Haikouella probably represents a very early craniate-like chordate that lived near the beginning of the Cambrian period during the main burst of the Cambrian explosion. These findings will add to the debate on the evolutionary transition from invertebrate to vertebrate.
Attainment of the biting jaw is regarded as one of the major novelties in the early history of vertebrates. Based on a comparison between lamprey and gnathostome embryos, evolutionary developmental studies have tried to explain this novelty as changes in the developmental patterning of the mandibular arch, the rostralmost pharyngeal arch, at the molecular and cellular levels. On the other hand, classical theories in the field of comparative morphology assumed the involvement of hypothetical premandibular arch(es) that ancestral animals would have possessed rostral to the mandibular arch, in the transition from agnathan to gnathostome states. These theories are highly biased toward the segmental scheme of the vertebrate head, and the concept of premandibular "arches" is no longer accepted by the current understanding. Instead, the premandibular domain has now become of interest in the understanding of cranial development, especially in its rostral part. As newer theories that consider involvement of the premandibular domain, the neoclassical and heterotopy theories are here compared from evolutionary developmental perspectives, in conjunction with the development of nasal and hypophyseal placodes, in the context of the evolutionary acquisition of the jaw. Given recent advances in understanding of the lamprey development, evolution of the Dlx code is also discussed together with the evolutionary scenario of jaw acquisition.