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Relations of Symmetry in the Developing Ear of Amblystoma Punctatum
... To establish a standardized schedule of developing processes, Harrison classified his embryos according to an embryonic staging table, which was also widely used by other researchers, but only published much later (Harrison 1969). Harrison explanted the otic placode or vesicle at various stages of development and re-implanted them into the same position on the same or contralateral side after rotation, thereby switching its orientation along the antero-posterior or the dorso-ventral axis or both (Harrison 1924;Harrison 1936). He found that the anteroposterior axis of the otic vesicle becomes fixed soon after neural tube closure (stage 21), well before the dorso-ventral axis was fixed at early tailbud stages (stage 23). ...
... At around the same time, experiments of Harrison's student Helen W. Kaan demonstrated that after extirpation of parts of the otic vesicle, normal inner ears of the proper size could form at least until later tailbud stages (stages 24/25) (Kaan 1927). At these stages, it is also still possible for a normal ear to develop after replacing the otic vesicle with two fused otic vesicles (Harrison 1936). This indicated that, like the limb bud, the otic vesicle of Ambystoma remains a "harmonic equipotential system" that is able to regulate its size and proper patterning until this stage. ...
As proposed by Wilhelm Roux in 1885, the key goal of experimental embryology (“Entwicklungsmechanik”) was to elucidate whether organisms or their parts develop autonomously (“self-differentiation”) or require interactions with other parts or the environment. However, experimental embryologists soon realized that concepts like “self-differentiation” only make sense when applied to particular parts or units of the developing embryo as defined both in time and space. Whereas the formation of tissues or organs may initially depend on interactions with surrounding tissues, they later become independent of such interactions or “determined.” Moreover, the determination of a particular tissue or organ primordium has to be distinguished from the spatially coordinated determination of its parts—what we now refer to as “patterning.” While some primordia depend on extrinsic influences (e.g., signals from adjacent tissues) for proper patterning, others rely on intrinsic mechanisms. Such intrinsically patterned units may behave as “morphogenetic fields” that can compensate for lost parts and regulate their size and proper patterning. While these insights were won by experimental embryologists more than 100 years ago, they retain their relevance today. To enable the generation of more life-like organoids in vitro for studying developmental processes and diseases in a dish, questions about the spatiotemporal units of development (when and how tissues and organs are determined and patterned) need to be increasingly considered. This review briefly sketches this conceptual history and its continued relevance by focusing on the determination and patterning of the inner ear with a specific emphasis on some studies published in this journal.
... Technical advantages of the chick include accessibility of the inner ear precursor (otocyst) to surgical manipulation and relative ease of young operated embryos to continue developing after surgery. Indeed, otocyst rotation surgery was performed in the 1930s (Harrison 1935) and used in the 1990s to study factors involved in inner ear development (e.g., Hutson et al. 1999; for review, see Wu and Kelley 2012). If the otocyst of 2-day-old chick embryos (E2) is surgically rotated 180°in ovo in the anterior-posterior and dorsal-ventral axes, with the medial-lateral axis fixed, a sac-like inner ear is formed with all three semicircular canals missing or truncated in 85% of cases (Lilian et al. 2019). ...
... Of apparent importance for induction and differentiation of the otic placode is the position with respect to the hindbrain, which, as already discussed in Section 2.2.2, is suggested to playa role in the induction and development of the ear (Harrison 1936;Yntema 1955;Van De Water 1983;Van De Water and Represa 1991). This topology can only be partly inferred from existing developmental data on a limited sample of vertebrate embryos. ...
Organogenesis of the vertebrate inner ear has been described as “one of the most remarkable displays of precision microengineering in the vertebrate body” (Swanson, Howard, and Lewis 1990). The initial morphological event in ear development in all vertebrates is the formation of the embryonic otic placode, a thickening of the head ectoderm in the region of the developing hindbrain. Through interaction with and incorporation of tissue from several other embryonic sources, the placode develops into the otocyst or otic vesicle, a differentiated structure with sharply defined borders (Noden and Van De Water 1986; Couly, Coltey, and Le Douarin 1993). The epithelium of the otic placode/vesicle also gives rise to the primary neurons of the statoacoustic ganglion, later in development called the cochleovestibular ganglion, the octaval, or the otic ganglion (probably the most appropriate terminology), which contributes to cranial nerve VIII and to the specialized sensory structures known as hair cells (Fig. 3.1).
... This is clearly seen in the placement of the vestibular apparatus, dorsally and the auditory portions ventrally, the generation of neurons from the anteriorventral regions of the otocyst or the formation of the endolymphatic duct from the medial otocyst. Experiments in which the otocyst is rotated with respect to its surrounding tissues, suggest that the patterning signals come from surrounding tissues [33][34][35]. These rotation experiments have suggested that the first to be fixed is the anterior-posterior axis. ...
The vertebrate inner ear hair cell can be considered as the apogee of cellular differentiation. It possesses apical modifications, the stereocilia and the kinocilia, that show remarkable sensitivity to the mechanical stimulation generated in the course of hearing or balance sensation. Understanding how these specializations occur would thus be a prerequisite to designing any cellular therapies to repair inner ear damage. In this chapter we describe the developmental decisions that a progenitor needs to make to become a hair cell and how these choices provide the context within which the mechanisms that lead to hair cell specialization can operate.
... Results just described support a long-held suspicion that the inner ear rudiment is at first equipotential along its A-P axis and later becomes compartmentalized about its A-P midline (Harrison 1936). Tbx1 may be one intrinsic component of a complex mechanism for converting a continuous gradient of RA into a binary state of the otocyst, namely its compartmentalization into anterior (neurogenic) and posterior (nonneurogenic) domains. ...
The vertebrate inner ear is composed of multiple sensory receptor epithelia, each of which is specialized for detection of sound, gravity, or angular acceleration. Each receptor epithelium contains mechanosensitive hair cells, which are connected to the brainstem by bipolar sensory neurons. Hair cells and their associated neurons are derived from the embryonic rudiment of the inner ear epithelium, but the precise spatial and temporal patterns of their generation, as well as the signals that coordinate these events, have only recently begun to be understood. Gene expression, lineage tracing, and mutant analyses suggest that both neurons and hair cells are generated from a common domain of neural and sensory competence in the embryonic inner ear rudiment. Members of the Shh, Wnt, and FGF families, together with retinoic acid signals, regulate transcription factor genes within the inner ear rudiment to establish the axial identity of the ear and regionalize neurogenic activity. Close-range signaling, such as that of the Notch pathway, specifies the fate of sensory regions and individual cell types. We also describe positive and negative interactions between basic helix-loop-helix and SoxB family transcription factors that specify either neuronal or sensory fates in a context-dependent manner. Finally, we review recent work on inner ear development in zebrafish, which demonstrates that the relative timing of neurogenesis and sensory epithelial formation is not phylogenetically constrained.
... In addition to interactions between NCC and neurons in development of the CV nerve, the proximity of the R4 NCC stream to the otic vesicle may be important for axial patterning of the inner ear. Inner ear patterning has been elucidated in large part by amphibian or chick experiments involving rotational transplants of otic placode, otic vesicle or hindbrain (Bok et al., 2005;Harrison, 1936;Wu et al., 1998). Rotational transplants of chick otic cup tissue at stages HH 10-12 (11 somites -16 somites) indicate that the anterior-posterior axis of the developing otic tissue is dictated by the host environment at that stage, and that the host influence is not mediated by the neural tube (Bok et al., 2005). ...
The cochleovestibular (CV) nerve, which connects the inner ear to the brain, is the nerve that enables the senses of hearing and balance. The aim of this study was to document the morphological development of the mouse CV nerve with respect to the two embryonic cells types that produce it, specifically, the otic vesicle-derived progenitors that give rise to neurons, and the neural crest cell (NCC) progenitors that give rise to glia. Otic tissues of mouse embryos carrying NCC lineage reporter transgenes were whole mount immunostained to identify neurons and NCC. Serial optical sections were collected by confocal microscopy and were compiled to render the three dimensional (3D) structure of the developing CV nerve. Spatial organization of the NCC and developing neurons suggest that neuronal and glial populations of the CV nerve develop in tandem from early stages of nerve formation. NCC form a sheath surrounding the CV ganglia and central axons. NCC are also closely associated with neurites projecting peripherally during formation of the vestibular and cochlear nerves. Physical ablation of NCC in chick embryos demonstrates that survival or regeneration of even a few individual NCC from ectopic positions in the hindbrain results in central projection of axons precisely following ectopic pathways made by regenerating NCC.
... Different otic axes appear to be established at different times in development. In the salamander, preplacodal transplantations revealed the AP axis is established first, and then followed by the DV axis (Harrison, 1936). A similar separation of axis establishment has been shown in the chick but at later developmental stages ( Wu et al., 1998). ...
Endogenous retinoic acid plays critical roles in normal vertebrate development, but can be teratogenic in excess. In mice, additional retinoic acid is administered by oral gavage or intraperitoneal injection. Here we evaluate a novel non-invasive system for administering retinoic acid via chocolate/sugar pellets. We use this delivery system to examine the role of retinoic acid in regulating the expression of the fibroblast growth factor Fgf3, and find that the timing of retinoic acid treatment is critical for its effects on Fgf3 expression. Administration of increasing amounts of retinoic acid at 7.75 dpc leads to dose-dependent downregulation of Fgf3 in the otocyst and changes in spatial expression in the hindbrain. Detailed analysis of the developing inner ear also reveals a lateralisation of Fgf3 expression with increasing retinoic acid dose that is dependent on timing of administration. We discuss how these data impact on current models of retinoic acid patterning of the otocyst.
Objective:
Polyotia is a very rare auricular malformation, and only few cases have been reported to date. Polyotia has been ambiguously defined, and due to the instability of its shape and condition, no uniform surgical technique has been established up to now. Thus, it is necessary to standardize the diagnosis and treatment of polyotia. The aim of the present study was to present a new set of objective diagnostic criteria for discussion, and introduce our surgical design for polyotia.
Methods:
A retrospective analysis was performed on 34 cases of polyotia, which were diagnosed and treated in our Plastic Surgery Department during a 3-year period from January 2016 to March 2019. The preoperative photographs, manifestations and operation records of these 34 cases were reviewed.
Results:
On the basis of the new set of objective diagnostic criteria, only 12 of 34 cases were diagnosed as polyotia, while the remaining 22 cases were diagnosed as accessory tragus. Polyotia was redefined as the presence of a broad-based accessory auricle in the tragus area along with accessory cavitas conchae similar to cavitas conchae. The new surgical design emphasized the use of cartilage and skin to fill up the concavity and reconstruct the tragus.
Conclusions:
The diagnosis of polyotia was presented on the basis of a new set of objective criteria, which include an accessory auricle and accessory cavitas conchae. The use of cartilage and skin to fill up the concavity and reconstruct the tragus were the emphases.
Many developmental disorders of the inner ear are manifested clinically as delayed motor development and challenges in maintaining posture and balance, indicating involvement of central vestibular circuits. How the vestibular circuitry is rewired in pediatric cases is poorly understood due to lack of a suitable animal model. Based on this, our lab designed and validated a chick embryo model to study vestibular development in congenital vestibular disorders. The developing inner ear or “otocyst” on the right side of 2-day-old chick embryos (E2) was surgically rotated 180° in the anterior–posterior axis, forming the “anterior–posterior axis rotated otocyst chick” or ARO chick. The ARO chick has a reproducible pathology of a sac with truncated or missing semicircular canals. A sac is the most common inner ear defect found in children with congenital vestibular disorders. In E13 ARO chicks, the sac contained all three cristae and maculae utriculi and sacculi, but the superior crista and macula utriculi were shortened in anterior–posterior extent. Also, the number of principal cells of the tangential vestibular nucleus, a major avian vestibular nucleus, was decreased 66 % on the rotated side. After hatching, no difference was detected between ARO and normal chicks in their righting reflex times. However, unlike normal chicks, ARO hatchlings had a constant, right head tilt, and after performing the righting reflex, ARO chicks stumbled and walked with a widened base. Identifying the structure and function of abnormally developed brain regions in ARO chicks may assist in improving treatments for patients with congenital vestibular disorder.
In vertebrates, perception of movement and sound is accomplished by the lateral line and inner ear sensory systems. These systems sense reverberations, movement and acceleration by transducing mechanical stimuli from the environment into electrical signals by means of mechanosensory hair cells. Vestibular and auditory hair cells have associated sensory neurons that transmit these signals from the periphery to the central nervous system. During development, cranial sensory systems arise from an initially homogeneous population of cells that ultimately give rise to discrete sensory structures. Although the demands for auditory and vestibular sensation differ between species and environments, vertebrates use common cell types, genetic programmes and molecules to achieve the development of these mechanosensory organs. In this article, the structure and function of the mechanosensory hair cells, lateral line and inner ear and how these systems develop across species are discussed, and as well as the innervation of these systems.
Key Concepts
The vertebrate inner ear is composed of both auditory and vestibular components.
Both the lateral line and the inner ear are derived from embryonic structures known as cranial placodes.
All cranial placodes originate from a homogenous group of cells known as the preplacodal ectoderm.
Hair cells are structurally and functionally similar in both auditory and lateral line systems.
The adult lateral line mediates sensation of movement in the aquatic environment of fishes and frogs.
Embryonic posterior lateral line development is accomplished by the pre‐patterned posterior lateral line primordium.
The lateral line is an experimentally accessible model for studying mechanosensory system development and biology.
The inner ear is a complex sensory organ essential for hearing and balance. During embryonic development, the inner ear depends on signaling information originating from the embryonic hindbrain to establish dorsoventral and anteroposterior identity. The Hedgehog (Hh) and Wnt signaling pathways are active in the hindbrain and implicated in otic development, but their exact mechanisms of action remained unclear. We investigated the function of Hh in ear development using a mouse model where we conditionally inactivated Hh signaling in the otic vesicle, a transient embryonic structure that gives rise to the inner ear, while leaving nearby Hh dependent tissues unaffected. We found Hh signaling within the otic vesicle functions to establish ventral otic identity and drive the proliferation of cochlear-vestibular ganglion (cvg) neuroblasts that will innervate the ear. We identified presumptive Hh target genes in the developing inner ear using microarrays. Several of these presumptive Hh targets are known to function in ear development or hearing. We also identified many novel targets that have not been characterized in the ear. Many of these novel presumptive Hh target genes are expressed in the ventral otic vesicle, a region that will give rise to the cochlear duct. To interrogate the function of Wnt signaling in ear development, we used a Wnt responsive inducible Cre recombinase (TopCreERT2) to genetically label cells at different stages of ear development. We found cells that make up dorsal, vestibular, structures and cvg neurons are Wnt responsive for prolonged periods of ear development. In the cochlear duct, we found both sensory and support cells originate from a Wnt responsive population. Surprisingly, we found the Wnt responsive population of cochlear progenitors was also labeled using a cre recombinase expressed from the Gbx2 locus. TopCreERT2 and Gbx2 expression overlap in the dorsomedial wall of the otic vesicle, suggesting this region is a likely source for auditory cells.
Taken as a developmental problem, the nervous system in higher metazoans represents the most complex example of pattern formation in all of biology. An understanding of the mechanisms regulating neural ontogeny cannot simply come from descriptive anatomy or physiology. As the early experimental embryologists realized, hypotheses about development may be born of observations on normal embryos, but experimental manipulations are necessary to prove them.1–3 The manipulations often take the classical form of tissue transplantation, and in the nervous system the results are analyzed with modern techniques of electrophysiology and neuroanatomical tracing. The power of combining these approaches has been enormously successful in generating basic rules of causal neurogenesis, even to the point of suggesting molecular mechanisms. Transplantation studies cannot, however, discover the molecules involved. The remarkable development of the topographic retinotectal projection as revealed by experimental manipulations in vivo has attracted many groups interested in the molecular biology of the formation of specific neural connections.4–9 If, as soon seems likely, theories derived from transplantation experiments are substantiated biochemically, it will constitute a major break-through in our understanding of the brain.
Remak’s legacy remains. “Ectoderm forms the outside, endoderm forms the inside, and mesoderm forms what’s in between” is the shorthand caricature of germ layers so often given to undergraduates. These are old ideas. We have known that embryos of animals such as the chick are built from three germ layers for 180 years, and that all vertebrates are built on a three-layered plan for 169 years. Huxley announced 148 years ago that two of the germ layers in vertebrate embryos’ectoderm and endoderm’are homologous to the two layers of adult coelenterates. Phyla have been classified as mono-, diplo-, or triploblastic, i.e., as having one, two, or three germ layers, for 124 years. Just as old is the germ-layer theory that homologous structures in different animals (must) arise from corresponding germ layers. Germ layers are part of the foundation of our understanding of animal organization.
The amphibian ear undergoes considerable structural and functional changes across metamorphosis, guided by many of the same molecular factors that underlie induction and morphogenesis in other vertebrates. Inner ear morphogenesis is complete before metamorphic climax, but the eight sensory organs follow separate timetables. The saccule segregates from the common macula and differentiates prior to the utricle and semicircular canals. The lagena, the amphibian papilla, and the basilar papilla are the last organs to differentiate. After metamorphosis, continued development is indexed by increases in sizes of the sensory epithelia, in hair cell numbers, and in numbers of myelinated eighth nerve axons. Middle ear pathways are not complete until after metamorphic climax. Neural processing in the central auditory and vestibular nuclei in tadpoles reflects the state of development of the saccule and the middle ear system. Vestibular-guided behaviors are present throughout larval development, but auditory-evoked behaviors have not been documented in tadpoles.
The published research of Ross Harrison, the inventor of tissue culture, and amongst the greatest of experimental embryologists, spans a period of 54 years. Before describing this immensely important contribution to biological knowledge, which must be the main concern of this memoir, the biographical framework in which it was made needs first to be sketched. Harrison was born on 13 January 1870, in Germantown (Philadelphia), Pennsylvania. His father, Samuel Harrison, was an engineer whose work took him for long periods abroad. His mother died when he was a child. After schooling in Baltimore, he entered Johns Hopkins University in 1886, somewhat undecided about his future. He recalls, in his Croonian Lecture, that it was Newell Martin, T. H. Huxley’s assistant and one of the original group of professors at Johns Hopkins, who first inspired him to become a zoologist. He started graduate work with W. K. Brooks, Martin’s successor, in 1889, amongst his fellow-students being two of his great contemporaries, E. G. Conklin and T. H. Morgan. He went abroad to work with Nussbaum in Bonn in 1892, establishing a connexion with German anatomists which was of great importance in his development. His Ph.D. at Hopkins followed in 1894, and after a year as Lecturer in Morphology at Bryn Mawr College, where T. H. Morgan had become Associate Professor of Biology, and another visit to Bonn, in 1896 he joined the staff of F. P. Mall, Professor of Anatomy at Johns Hopkins and a distinguished embryologist. In 1896 he married Ida Lange, whom he had met on his first visit to Bonn. They had a family of three daughters and two sons. He returned briefly to Bonn twice before the end of the century, and took his M.D. there in 1899, the same year that he became Associate Professor of Anatomy at Johns Hopkins. He stayed a further eight years in Baltimore, and this was the period of his momentous invention of tissue culture. The brilliance of this research is all the more astonishing in that he was at this same time launching and guiding, as managing editor, the new Journal of Experimental Zoology ; and as he later ruefully remarked, in those days the editor of a scientific journal had to be business manager and office boy as well.
This chapter discusses that within the conceptual framework of positional information, a new and a simple way of looking at pattern formation may be obtained. In pressing the possibility of universality, the chapter deliberately takes an extreme stand, but at least it serves to counterbalance the special-substance inductive view of pattern formation. Also, in order to show its possible relevance to pattern formation and even cell movement, procrustean view of the data is taken. One of the virtues of the positional information mechanism of pattern formation is that, with the same system for positional information one can generate an enormous number of different patterns, by changing the cell's rules for interpretation. Since interpretation will be gene determined, there is little difficulty in seeing how this can be achieved. In fact, the concept of positional information makes excellent use of a central feature of development, that all the cells carry the same genetic information.
Twelfth gestation day kreisler otocysts were explanted into an organ culture system and allowed to develop for nine days. The homozygotic (kr/kr) kreisler otocysts showed significant developmental differences when compared to the development that occurred in the organ culture specimens of the otocysts of its heterozygotic (+ /kr) litter mates. The differences in development observed in vitro were the same major developmental differences that had been observed in vivo. The phenotypic expression of the kreisler genome has expressed itself in vitro in the homozygotic kreisler otocyst.
The retinotectal projection was mapped electrophysiologically in 67 experiments on Ranu temporaria at various intervals (from 23 to 247 days) after section of the optic nerve. In 18 animals regeneration had not occurred at the time of recording; in the others the projections could be classified in the following way, according to the degree of normality of the pattern: Pattern 1: In 14 frogs there was disorganized anomalous regeneration from small regions of the retina. Tectal responses could not be evoked from the normal stimulus positions but could be evoked only from one or two localized regions of visual field. In 8 of these frogs there was one circumscribed region in the nasal half of the field and another in the temporal half from which responses could be obtained; in 4 animals there was only one region, in the nasal field, and in 2 animals there was one region, in the temporal field, from which tectal responses could be evoked. The earliest responses recorded after nerve section were of pattern 1. Pattern 2: In 4 frogs there was an abnormal projection showing partial organization in only one axis of the retina (nasotemporal, circumferential) and in only one axis of the tectum (mediolateral). This partial organization was only found at the rostral end of the tectum. Pattern 3: In 12 frogs there was recovery of the normal retinotectal projection. Pattern 4: In 15 frogs there was partial or complete recovery of the normal projection together with an anomalous but retinotopically organized projection to the wrong half to the brain. This latter projection was organized as a mirror image of the normal ipsilateral projection. One frog combined the elements of patterns 1 and 4 and the remaining 3 animals did not conform to any of the above patterns. Most of the negative results were obtained in the early days after nerve section and all recordings made later than 77 days after section gave responses. Patterns 3 and 4 were obtained more frequently the longer the interval between nerve section and recording.
Why study the vertebrate auditory system? Throughout the ages, when scholars have attempted to define objectively the qualities that distinguish man from other animals, the power of human communication systems inevitably comes to the fore. Normal development of auditory perception is essential for the establishment of both expressive and receptive aspects of language. Thus, increased understanding, leading to eventual prevention or treatment of the various conditions that cause failures in the normal processing of acoustic information, has important clinical relevance. Furthermore, the auditory system is one of the primary sense modalities, involving both a highly specialized peripheral receptor organ and a complex set of central pathways.
Several studies have demonstrated that rotated segments of the embryonic hindbrain will repolarize to conform with the host gradients, and that the developing Mauthner (M-) axons reorient accordingly, tending to follow a normal course. To investigate the response of these axons to an irreversibly antagonistic polarity, we prepared Janus-headed telobionts in which initially descending M-fibers would begin to ascend upon entering the opposite head. About one-third of the fibers became disoriented within the graft region, evidently as a result of inadequate healing. The remaining two-thirds traversed the graft and continued to ascend the opposite head past the medulla and into the midbrain and forebrain. The apparent ease with which these M-axons made their way upgradient may have been enhanced by (1) inability of growth cones to respond to head-on gradients; (2) selective fasciculation; (3) weakening of the rostrocaudal (longitudinal) gradients as a result of birostral telobiosis; and (4) growth through intact tissue.
Most of these M-axons negotiated a rostrocaudal polar inversion in much the same way as commissural fibers normally do in passing from lateral to medial, then from medial to lateral. We suggest that crossing fibers may be impeded by their encounter with the contralateral antagonistic gradient, and that for this reason the rostrocaudal directional tendencies of decussating axons are expressed only after the midline has been crossed. This hypothesis does not require assumptions of right-left specificity or intricately coordinated timing of developmental events to explain decussation.
An experiment was undertaken to determine which sensory structures of the mouse embryo inner ear developed from what portion of the mouse otocyst. Otocysts of gestation days 10, 11, 12 and 13 were divided by surgical dissection into six anatomical groups: dorsal, ventral, anterior, posterior, medial and lateral halves. They were organ cultured separately. After a period of ten days, the explanted tissues were harvested and processed histologically for microscopic analysis. The surgical control specimens fixed at the time of explanation were composed of undifferentiated ectodermal cells for tissues of gestation days 10, 11, and 12. Otocysts of gestation day ten showed no gross morphological differentiation. Otocysts of gestation days 11 and 12 showed, during the course of their subsequent growth, that the three semicircular ducts and their associated cristae developed from the dorsal and lateral halves. Only the anterior and posterior canals and cristae originated from the medial portion. The posterior half gave rise to the posterior crista and the anterior half provided for the development of the anterior and lateral cristae. The cochlear duct and its sensory epithelium developed in all the anatomical groups except the dorsal half. The utricle developed in the dorsal section of the middle third of the otocyst, while the utricular macula developed in the anterior half of the same section of the otocyst. The saccule and its macula differentiated from the ventral section of the middle third of the anterior half.
Early regionalized gene expression patterns within the otocyst appear to correlate with and contribute to development of mature otic structures. In the chick, the transcription factor Pax2 becomes restricted to the dorsal and entire medial side of the otocyst by stage 16/17. The dorsal region of the otocyst forms the endolymphatic duct and sac (ED/ES), and the cochlear duct is derived from the ventromedial region. In the mouse, however, Pax2 expression is reported only in the ventromedial and not the dorsal otocyst. In Pax2 null mice, the cochlea is missing or truncated, but vestibular structures differentiate normally. Here we demonstrate that in the chick, the emerging ED/ES express high levels of Pax2 even when the position of the emerging ED is altered with respect to its environment, either by 180 otocyst rotations about the anterior/posterior axis or transplantation of the otocyst into the hindbrain cavity. However, the Pax2 expression pattern is plastic in the rest of the otic epithelium after 180 rotation of the otocyst. Pax2 is upregulated on the medial side (formerly lateral), and downregulated on the lateral side (formerly medial and expressing Pax2) indicating that Pax2 expression is influenced by the environment. Although Pax2 is upregulated in the epithelium after 180 rotations in the region that should form the cochlear duct, cochlear ducts are truncated or absent, and the ED/ES emerge in a new ventrolateral position. Ablation of the hindbrain at the placode or early otic pit stage alters the timing of regionalized Pax2 expression in the otocyst. The resulting otocysts and ears are generally smaller, vestibular structures are abnormal, ED/ES are missing but cochlear ducts are of normal length. The hindbrain and dorsal periotic mesenchyme provide unique trophic and patterning information to the dorsal otocyst. Our results demonstrate that the ED is the earliest structure patterned in the inner ear and that the hindbrain is important for its specification. We also show that, although normal Pax2 expression is required for cochlear duct development, it is downstream of ventral otocyst patterning events.
Retinal ganglion cells ofXenopus form topographically organized connections with the optic tectum between larval stages 35 and 40. However, the position at which each retinal ganglion cell connects in the tectum is already fully specified at larval stage 31, before visible differentiation of ganglion cells and before outgrowth of their axons. This was shown by 180-degree rotation of the eyecup ofXenopus larvae at stages 28–35. After metamorphosis of these animals, the projection from the rotated eye to the optic tectum was mapped electrophysiologically, and compared with the normal retinotectal map.Normal retinotectal connections were formed after rotation of the eyecup before stage 30. Eye rotation at stage 30 resulted in reversal of the retinotectal map in the AP axis, but not in the DV axis of the retina. Rotation of the eye after stage 30 resulted in total rotation of the retinotectal map.Specification of the central connections of retinal ganglion cells occurs over a period of about 10 hours, in two steps related to the relative positions of the ganglion cells in the AP and DV axes of the retina. The hypothesis is advanced of stepwise specification of progressively finer details of the pattern of neuronal connections; the initial steps occurring at an early stage of neuroblast differentiation before the outgrowth of neuronal processes.
Homeobox-containing genes encode a class of proteins that control patterning in developing systems, in some cases by acting as selector genes that define compartment identity. In an effort to demonstrate a similar role for such genes during ear development in the chicken, we present a detailed expression study of two related homeobox-containing genes,SOHo-1andGH6,usingin situhybridization. At otocyst stages the two genes define a broad lateral domain of expression, which may represent a developmental compartment. Three-dimensional computer reconstructions ofSOHo-1expression at these and later stages revealed that the lateral domain becomes progressively restricted to the three semicircular canals. Thus,SOHo-1andGH6are among a small group of markers for a specific structural component of the inner ear. The gene expression domain initially includes the sensory regions of the semicircular canals, known as the cristae ampullaris, but none of the other four sensory organs which were recognizable byBMP4expression during early morphogenesis (stages 19–24). Significantly, two of the sensory organs (the superior and posterior cristae) were found at the limits, or boundaries, of theSOHo-1/GH6expression domain, suggesting that compartment boundaries may be involved in specifying sensory organ location as well as identity. Maintained expression at the boundaries may aid in specifying the location of canal outgrowth. These concepts are presented as a formal model which emphasizes that patterning information could be provided at the boundaries of gene expression domains in the inner ear.
The inner ear is one of the most morphologically elaborate tissues in vertebrates, containing a group of mechanosensitive sensory organs that mediate hearing and balance. These organs are arranged precisely in space and contain intricately patterned sensory epithelia. Here, we review recent studies of inner ear development and patterning which reveal that multiple stages of ear development - ranging from its early induction from the embryonic ectoderm to the establishment of the three cardinal axes and the fine-grained arrangement of sensory cells - are orchestrated by gradients of signaling molecules.
112 minutes instead of
The scale of the abscissa should read:
5, 23, 40, 58,
76, 94,
112 minutes
instead of, 0, 1/2, 1, 11/2, 2, 21/2,
3 hours.
W. G. CLARK
VOL. 22, 1936
- M H Choi
- Fol
- Ana
Choi, M. H., Fol. Ana. Jap., 9, 315-332 (1931); Id., Jour. Severance Union Med.
- C Ogawa
6 Ogawa, C., Jour. Exp. Zool., 34, 17-43 (1921); Id., Fol. Anat. Jap., 4, 413-431
(1926).
Note on the Effect of Light on the Bioelectric Potentials in the Avena Coleoptile the following changes should be made: page 682, Upper graph of figure 1. 1. Illumination should be 800
- Erra Ta In The
ERRA TA
In the "Note on the Effect of Light on the Bioelectric Potentials in the
Avena Coleoptile" in these PROCEEDINGS, 21, December, 1935, pp. 681-
684, the following changes should be made:
page 682, Upper graph of figure 1.
1. Illumination should be 800,000 instead of 80,OOOMCS.
- H Spemann
Spemann, H., Arch. Entw.-Mech., 123, 389-517 (1931);
- G Ruud
Ruud, G., Jour. Exp. Zool., 46, 121-142 (1926);
); see also the somewhat divergent results of Woerdeman
- Is Twitty
- V C Ibid
Is Twitty, V. C., Ibid., 50, 319-344 (1928); see also the somewhat divergent results
of Woerdeman, N. W., Arch. Entw.-Mech., 106, 41-61 (1925).
14 Stone, L. S., Science, 74, 577 (1931).
- R G Harrison
- Exp Jour
- W Brandt
Harrison, R. G., Jour. Exp. Zool., 32, 1-136 (1921); Brandt, W., Arch. mikr. Anat.