NDLI: Otic ablation of smoothened reveals direct and indirect requirements for Hedgehog signaling in inner ear development

Content Provider	PubMed Central
Author	Brown, Alexander S. Epstein, Douglas J.
Abstract	In mouse embryos lacking sonic hedgehog (Shh), dorsoventral polarity within the otic vesicle is disrupted. Consequently, ventral otic derivatives, including the cochlear duct and saccule, fail to form, and dorsal otic derivatives, including the semicircular canals, endolymphatic duct and utricle, are malformed or absent. Since inner ear patterning and morphogenesis are heavily dependent on extracellular signals derived from tissues that are also compromised by the loss of Shh, the extent to which Shh signaling acts directly on the inner ear for its development is unclear. To address this question, we generated embryos in which smoothened (Smo), an essential transducer of Hedgehog (Hh) signaling, was conditionally inactivated in the otic epithelium (Smoecko ). Ventral otic derivatives failed to form in Smoecko embryos, whereas vestibular structures developed properly. Consistent with these findings, we demonstrate that ventral, but not dorsal, otic identity is directly dependent on Hh. The role of Hh in cochlear-vestibular ganglion (cvg) formation is more complex, as both direct and indirect signaling mechanisms are implicated. Our data suggest that the loss of cvg neurons in Shh–/– animals is due, in part, to an increase in Wnt responsiveness in the otic vesicle, resulting in the ectopic expression of Tbx1 in the neurogenic domain and subsequent repression of Ngn1 transcription. A mitogenic role for Shh in cvg progenitor proliferation was also revealed in our analysis of Smoecko embryos. Taken together, these data contribute to a better understanding of the intrinsic and extrinsic signaling properties of Shh during inner ear development.
Related Links	http://dx.doi.org/10.1242/dev.066126
Ending Page	3976
Page Count	10
Starting Page	3967
File Format	PDF
ISSN	09501991
e-ISSN	14779129
Journal	Development (Cambridge, England)
Issue Number	18
Volume Number	138
Language	English
Publisher	Company of Biologists
Publisher Date	2011-09-15
Access Restriction	Open
Rights Holder	Company of Biologists
Subject Keyword	Developmental Biology Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Developmental Biology Molecular Biology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Hedgehog signalling is required for correct anteroposterior patterning of the zebrafish otic vesicle

Gbx2 is required for the morphogenesis of the mouse inner ear: a downstream candidate of hindbrain signaling

Changes in retinoic acid signaling alter otic patterning

Requirements for FGF3 and FGF10 during inner ear formation

Zebrafish con/disp1 reveals multiple spatiotemporal requirements for Hedgehog-signaling in craniofacial development

Direct and indirect requirements of Shh/Gli signaling in early pituitary development

Smoothened Goes Molecular: New Pieces in the Hedgehog Signaling Puzzle

Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened

Compensatory regulation of the size of the inner ear in response to excess induction of otic progenitors by FGF signaling

Otic ablation of smoothened reveals direct and indirect requirements for Hedgehog signaling in inner ear development

Similar Documents

Hedgehog signalling is required for correct anteroposterior patterning of the zebrafish otic vesicle

Gbx2 is required for the morphogenesis of the mouse inner ear: a downstream candidate of hindbrain signaling

Changes in retinoic acid signaling alter otic patterning

Requirements for FGF3 and FGF10 during inner ear formation

Zebrafish con/disp1 reveals multiple spatiotemporal requirements for Hedgehog-signaling in craniofacial development

Direct and indirect requirements of Shh/Gli signaling in early pituitary development

Smoothened Goes Molecular: New Pieces in the Hedgehog Signaling Puzzle

Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened

Compensatory regulation of the size of the inner ear in response to excess induction of otic progenitors by FGF signaling

Otic ablation of smoothened reveals direct and indirect requirements for Hedgehog signaling in inner ear development