Temporospatial sonic hedgehog signalling is essential for neural crest-dependent patterning of the intrinsic tongue musculature.
Development
; 146(21)2019 11 12.
Article
en En
| MEDLINE
| ID: mdl-31719045
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Lengua
/
Transducción de Señal
/
Tipificación del Cuerpo
/
Proteínas Hedgehog
/
Cresta Neural
Límite:
Animals
Idioma:
En
Revista:
Development
Asunto de la revista:
BIOLOGIA
/
EMBRIOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Japón