Ablation studies on the developing inner ear reveal a propensity for mirror duplications

Waldman, Erik H.; Castillo, Aldo; Collazo, Andrés

doi:10.1002/dvdy.21144

Cited by 18 publications

(49 citation statements)

References 50 publications

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“…2). A recent study has reported a very similar finding in Xenopus : here, injection of mRNA coding for the Hh inhibitor Hip results in mirror image duplications of anterior inner ear structures (Waldman et al, 2007). When the Hh pathway is activated ectopically in the zebrafish, by injection of shh or dominant negative PKA RNA, we see the reverse phenotype: ears lose anterior otic structures and show a mirror image duplication of posterior regions (Hammond et al, 2003) (Fig.…”

Section: Role Of the Midline In Otic Ap Patterningsupporting

confidence: 73%

“…These enantiomorphic phenotypes demonstrate that the A and P poles of the ear initially have the potential to form either A or P structures; they are reminiscent of other classical developmental axial duplications, such as those of the chick limb following transplantation of the zone of polarising activity, or Drosophila segment polarity phenotypes. Double anterior or posterior ears can also result during regeneration of otic tissue after partial ablation of the placode in Xenopus : these phenotypes are strikingly similar to those generated by the salamander rotation experiments or by manipulations of Hh signalling in zebrafish (Waldman et al, 2007) (Fig. 2J-O).…”

Section: Equipotentiality About the Ap Axis Of The Otic Placode And Vsupporting

confidence: 62%

“…2A-C). Similarly, manipulation of the Hedgehog (Hh) signalling pathway in the fish and amphibian embryo can also result in double anterior or double posterior ears (Hammond et al, 2003;Waldman et al, 2007) (Fig. 2D-I; see further discussion in the section on AP patterning below).…”

Section: Equipotentiality About the Ap Axis Of The Otic Placode And Vmentioning

confidence: 99%

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Axial patterning in the developing vertebrate inner ear

Whitfield

Hammond²

2007

Int. J. Dev. Biol.

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Axial patterning in the vertebrate inner ear has been studied for over eighty years, and recent work has made great progress towards an understanding of the molecular mechanisms responsible for establishing asymmetries about the otic axes. Tissues extrinsic to the ear provide sources of signalling molecules that are active early in development, at or before otic placode stages, while intrinsic factors interpret these signals to establish and maintain axial pattern. Key features of dorsoventral otic patterning in amniote embryos involve Wnt and Fgf signalling from the hindbrain and Hh signalling from midline tissues (notochord and floorplate). Mutual antagonism between these pathways and their downstream targets within the otic epithelium help to refine and maintain dorsoventral axial patterning in the ear. In the zebrafish ear, the same tissues and signals are implicated, but appear to play a role in anteroposterior, rather than dorsoventral, otic patterning. Despite this paradox, conservation of mechanisms may be higher than is at first apparent.

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Section: Role Of the Midline In Otic Ap Patterningsupporting

confidence: 73%

Section: Equipotentiality About the Ap Axis Of The Otic Placode And Vsupporting

confidence: 62%

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Axial patterning in the developing vertebrate inner ear

Whitfield

Hammond²

2007

Int. J. Dev. Biol.

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“…These mirror image duplications suggest that the inner ear rudiment is at first equipotential along the A-P axis and later compartmentalized about its A-P midline. In recent years, similar mirror image duplications of inner ears in zebrafish and frogs have also been reported from perturbing hedgehog (hh) signaling (26,27). Paradoxically, hedgehog signaling does not appear to be a primary determinant for A-P patterning of the inner ear in amniotes, even though it is essential for the dorsal-ventral (D-V) patterning (4,28,29).…”

Section: Discussionmentioning

confidence: 93%

Transient retinoic acid signaling confers anterior-posterior polarity to the inner ear

Bok

Raft

Kong

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

103

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Vertebrate hearing and balance are based in complex asymmetries of inner ear structure. Here, we identify retinoic acid (RA) as an extrinsic signal that acts directly on the ear rudiment to affect its compartmentalization along the anterior-posterior axis. A rostrocaudal wave of RA activity, generated by tissues surrounding the nascent ear, induces distinct responses from anterior and posterior halves of the inner ear rudiment. Prolonged response to RA by posterior otic tissue correlates with Tbx1 transcription and formation of mostly nonsensory inner ear structures. By contrast, anterior otic tissue displays only a brief response to RA and forms neuronal elements and most sensory structures of the inner ear.axial specification | developmental compartments | morphogen N ormal hearing and balance require that discrete patches of mechanosensory hair cells, each with a distinct function, be precisely positioned within the asymmetric membranous labyrinth of the inner ear (Fig. 1A). Five vestibular sensory patches are present in all vertebrate inner ears: the three cristae (anterior, lateral, and posterior) that detect angular head movements and two maculae (utricle and saccule) that detect linear acceleration. The specialized organ for detecting sound in chickens and mammals is the basilar papilla and organ of Corti, respectively.The entire membranous labyrinth and its innervating neurons are derived from an ectodermal thickening adjacent to the hindbrain known as the otic placode. As the placode deepens to form a cup and then pinches off to form the otocyst, some cells of the otic epithelium delaminate to form neuroblasts of the cochleovestibular ganglion (CVG). Inner ear sensory organs, and the neurons that innervate them, are thought to arise from a neural-sensory competent domain (NSD), most of which is located in the anterior region of the otic cup (1). By contrast, posterior otic epithelium forms nonsensory tissues and only one sensory organ, the posterior crista. This basic organization of functional elements in the ear is thought to be governed by signals emanating from adjacent tissues (2, 3); however, molecular mechanisms that establish the initial anterior-posterior (A-P) asymmetry of the ear primordium are poorly defined. Here, we show that a rostrocaudal wave of retinoic acid activity provides signals to the ear rudiment and establishes structural asymmetries required for normal hearing and balance. ResultsEctoderm Adjacent to the Otic Cup Confers A-P Polarity to the Otocyst. A clear manifestation of A-P asymmetry in developing amniote ears is the anterior expression of transcripts associated with cochleovestibular ganglion neurogenesis. We performed tissue transplantations in ovo to identify source(s) of signals that specify the otic A-P axis in the chicken. Transplantations were carried out at the otic cup stage (11-15 somite stages), before the otic A-P axis is specified (4). As expected, reversing the A-P orientation of the otic cup alone resulted in a high occurrence of otocysts with the axial plan...

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“…The abilities of Xenopus to elucidate the cellular and molecular aspects of developmental processes position it as a valuable model organism (5)(6)(7). Earlier studies of lineage analysis and spatiotemporal expression of transcription factors during inner ear development led to construction of an inner ear fate map in Xenopus and this fate map allows us to interpret gene expression patterns within the context of the anatomy (8,9).…”

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confidence: 99%

Sp8 regulates inner ear development

Chung

Medina-Ruiz

Harland

2014

Proc. Natl. Acad. Sci. U.S.A.

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A forward genetic screen of N-ethyl-N-nitrosourea mutagenized Xenopus tropicalis has identified an inner ear mutant named eclipse (ecl). Mutants developed enlarged otic vesicles and various defects of otoconia development; they also showed abnormal circular and inverted swimming patterns. Positional cloning identified specificity protein 8 (sp8), which was previously found to regulate limb and brain development. Two different loss-of-function approaches using transcription activator-like effector nucleases and morpholino oligonucleotides confirmed that the ecl mutant phenotype is caused by down-regulation of sp8. Depletion of sp8 resulted in otic dysmorphogenesis, such as uncompartmentalized and enlarged otic vesicles, epithelial dilation with abnormal sensory end organs. When overexpressed, sp8 was sufficient to induce ectopic otic vesicles possessing sensory hair cells, neurofilament innervation in a thickened sensory epithelium, and otoconia, all of which are found in the endogenous otic vesicle. We propose that sp8 is an important factor for initiation and elaboration of inner ear development.T he vertebrate inner ear is a sensory organ responsible for balance and sound detection. Dysfunction of the inner ear is among the most common congenital disorders, affecting at least 1 in 500 births (1) and ∼40% of sensorineural deafness is associated with inner ear malformations (2). However, the study of hearing and balance impairment in humans is limited by the inability to follow inner ear development. Vertebrates share similarities in the sequence of developmental events that form the inner ear: the formation of an otic placode from an ectodermal thickening, morphogenesis to form the otocyst, and regional patterning of the otic vesicle (OV), resulting in the 3D membranous labyrinth (3, 4). Multipotent sensory progenitor cells are induced in the ectoderm surrounding the anterior neural plate, a domain termed the preplacodal region (PPR), and six1 has been characterized as marking this panplacodal domain. Signals from hindbrain and the regional expression of different transcription factors differentiate the PPR into the otic placode. The OV is partitioned by asymmetrical expression of various developmental regulators to pattern subdomains of the developing inner ear.The abilities of Xenopus to elucidate the cellular and molecular aspects of developmental processes position it as a valuable model organism (5-7). Earlier studies of lineage analysis and spatiotemporal expression of transcription factors during inner ear development led to construction of an inner ear fate map in Xenopus and this fate map allows us to interpret gene expression patterns within the context of the anatomy (8, 9). In recent years, genetic and genomic approaches have been developed in Xenopus tropicalis (10-13). To advance our understanding of inner ear development, we have screened N-ethyl-N-nitrosourea (ENU) mutagenized X. tropicalis colonies and recovered an inner ear mutant named eclipse (ecl). The ecl mutant perturbs specificity protei...

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Ablation studies on the developing inner ear reveal a propensity for mirror duplications

Cited by 18 publications

References 50 publications

Axial patterning in the developing vertebrate inner ear

Axial patterning in the developing vertebrate inner ear

Transient retinoic acid signaling confers anterior-posterior polarity to the inner ear

Sp8 regulates inner ear development

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