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Temporospatial sonic hedgehog signalling is essential for neural crest-dependent patterning of the intrinsic tongue musculature.

Authors :
Okuhara S
Birjandi AA
Adel Al-Lami H
Sagai T
Amano T
Shiroishi T
Xavier GM
Liu KJ
Cobourne MT
Iseki S
Source :
Development (Cambridge, England) [Development] 2019 Nov 12; Vol. 146 (21). Date of Electronic Publication: 2019 Nov 12.
Publication Year :
2019

Abstract

The tongue is a highly specialised muscular organ with a complex anatomy required for normal function. We have utilised multiple genetic approaches to investigate local temporospatial requirements for sonic hedgehog (SHH) signalling during tongue development. Mice lacking a Shh cis -enhancer, MFCS4 ( ShhMFCS4/- ), with reduced SHH in dorsal tongue epithelium have perturbed lingual septum tendon formation and disrupted intrinsic muscle patterning, with these defects reproduced following global Shh deletion from E10.5 in pCag - CreERTM; Shhflox/flox embryos. SHH responsiveness was diminished in local cranial neural crest cell (CNCC) populations in both mutants, with SHH targeting these cells through the primary cilium. CNCC-specific deletion of orofaciodigital syndrome 1 ( Ofd1 ), which encodes a ciliary protein, in Wnt1-Cre; Ofdfl/Y mice led to a complete loss of normal myotube arrangement and hypoglossia. In contrast, mesoderm-specific deletion of Ofd1 in Mesp1-Cre; Ofdfl/Y embryos resulted in normal intrinsic muscle arrangement. Collectively, these findings suggest key temporospatial requirements for local SHH signalling in tongue development (specifically, lingual tendon differentiation and intrinsic muscle patterning through signalling to CNCCs) and provide further mechanistic insight into the tongue anomalies seen in patients with disrupted hedgehog signalling.<br />Competing Interests: Competing interestsThe authors declare no competing or financial interests.<br /> (© 2019. Published by The Company of Biologists Ltd.)

Details

Language :
English
ISSN :
1477-9129
Volume :
146
Issue :
21
Database :
MEDLINE
Journal :
Development (Cambridge, England)
Publication Type :
Academic Journal
Accession number :
31719045
Full Text :
https://doi.org/10.1242/dev.180075