Canonical Wnt signaling regulates soft palate development by mediating ciliary homeostasis

© 2023. Published by The Company of Biologists Ltd..

Craniofacial morphogenesis requires complex interactions involving different tissues, signaling pathways, secreted factors and organelles. The details of these interactions remain elusive. In this study, we have analyzed the molecular mechanisms and homeostatic cellular activities governing soft palate development to improve regenerative strategies for individuals with cleft palate. We have identified canonical Wnt signaling as a key signaling pathway primarily active in cranial neural crest (CNC)-derived mesenchymal cells surrounding soft palatal myogenic cells. Using Osr2-Cre;β-cateninfl/fl mice, we show that Wnt signaling is indispensable for mesenchymal cell proliferation and subsequently for myogenesis through mediating ciliogenesis. Specifically, we have identified that Wnt signaling directly regulates expression of the ciliary gene Ttll3. Impaired ciliary disassembly leads to differentiation defects in mesenchymal cells and indirectly disrupts myogenesis through decreased expression of Dlk1, a mesenchymal cell-derived pro-myogenesis factor. Moreover, we show that siRNA-mediated reduction of Ttll3 expression partly rescues mesenchymal cell proliferation and myogenesis in the palatal explant cultures from Osr2-Cre;β-cateninfl/fl embryos. This study highlights the role of Wnt signaling in palatogenesis through the control of ciliary homeostasis, which establishes a new mechanism for Wnt-regulated craniofacial morphogenesis.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:150

Enthalten in:

Development (Cambridge, England) - 150(2023), 5 vom: 01. März

Sprache:

Englisch

Beteiligte Personen:

Janečková, Eva [VerfasserIn]
Feng, Jifan [VerfasserIn]
Guo, Tingwei [VerfasserIn]
Han, Xia [VerfasserIn]
Ghobadi, Aileen [VerfasserIn]
Araujo-Villalba, Angelita [VerfasserIn]
Rahman, Md Shaifur [VerfasserIn]
Ziaei, Heliya [VerfasserIn]
Ho, Thach-Vu [VerfasserIn]
Pareek, Siddhika [VerfasserIn]
Alvarez, Jasmine [VerfasserIn]
Chai, Yang [VerfasserIn]

Links:

Volltext

Themen:

Ciliogenesis
Journal Article
Palatogenesis
Research Support, N.I.H., Extramural
Soft palate development
Wnt signaling

Anmerkungen:

Date Completed 14.03.2023

Date Revised 10.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1242/dev.201189

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM353322016