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PMID: 12231626 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Specification of the mammalian cochlea is dependent on Sonic hedgehog.

Genes & development ·Vol. 16 ·No. 18 ·2002-09-15 ·Pages 2365-78

Riccomagno MM, Martinu L, Mulheisen M, Wu DK, Epstein DJ

Abstract

Organization of the inner ear into auditory and vestibular components is dependent on localized patterns of gene expression within the otic vesicle. Surrounding tissues are known to influence compartmentalization of the otic vesicle, yet the participating signals remain unclear. This study identifies Sonic hedgehog (Shh) secreted by the notochord and/or floor plate as a primary regulator of auditory cell fates within the mouse inner ear. Whereas otic induction proceeds normally in Shh(-/-) embryos, morphogenesis of the inner ear is greatly perturbed by midgestation. Ventral otic derivatives including the cochlear duct and cochleovestibular ganglia failed to develop in the absence of Shh. The origin of the inner ear defects in Shh(-/-) embryos could be traced back to alterations in the expression of a number of genes involved in cell fate specification including Pax2, Otx1, Otx2, Tbx1, and Ngn1. We further show that several of these genes are targets of Shh signaling given their ectopic activation in transgenic mice that misexpress Shh in the inner ear. Taken together, our data support a model whereby auditory cell fates in the otic vesicle are established by the direct action of Shh.

MeSH Terms
Animals Body Patterning/genetics,physiology Cochlea/embryology DNA-Binding Proteins/genetics Ear, Inner/abnormalities,embryology Ganglia/embryology Gene Expression Regulation, Developmental Hedgehog Proteins Mice Mice, Knockout Mice, Transgenic Models, Biological PAX2 Transcription Factor Signal Transduction Trans-Activators/deficiency,genetics,physiology Transcription Factors/genetics Tretinoin/pharmacology
Chemicals
DNA-Binding Proteins Hedgehog Proteins PAX2 Transcription Factor Pax2 protein, mouse Trans-Activators Transcription Factors Tretinoin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Riccomagno Martin M
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Martinu Lenka
Mulheisen Michael
Wu Doris K
Epstein Douglas J
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1013302
Published
2002-09-15
Pages
2365-78
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC187441
Subset
IM
Grants
NINDS NIH HHS · R01 NS039421 · United States
NINDS NIH HHS · R01 NS39421 · United States
External Links
PubMed source DOI: 10.1101/gad.1013302 PMC Full Text View journal details
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