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G-Protein α-Subunit Gsα Is Required for Craniofacial Morphogenesis
Run Lei1,2,3, Ke Zhang1,2,3, Yanxia Wei1
1West China Developmental & Stem Cell Institute, West China Second Hospital, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Plos One
|February 10, 2016
Summary
The G protein subunit Gsα is crucial for craniofacial development in neural crest cells (NCCs). Loss of Gsα in NCCs leads to severe craniofacial defects and impaired ganglion development in mice.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- The heterotrimeric G protein subunit Gsα activates adenylyl cyclase, mediating cyclic AMP (cAMP) signaling and protein kinase A (PKA) activation.
- Gsα is widely expressed, but its specific function in neural crest cells (NCCs) is not well understood.
Purpose of the Study:
- To investigate the role of Gsα in the development of NCCs and their derivatives.
- To elucidate the impact of Gsα deficiency on craniofacial and peripheral nervous system development.
Main Methods:
- Generation of NCCs-specific Gsα knockout mice.
- Histological and anatomical analyses of craniofacial structures and peripheral ganglia.
- Assessment of NCC migration, proliferation, and differentiation.
Main Results:
- NCC-specific Gsα knockout mice exhibit perinatal lethality and severe craniofacial malformations, including hypoplastic maxilla/mandible and cleft palate.
- Cleft palate is a secondary defect stemming from craniofacial skeleton deficiencies.
- While cranial nerve morphology is normal, dorsal root and sympathetic ganglia development is impaired.
- Loss of Gsα in NCCs accelerates osteochondrogenic differentiation but does not affect NCC migration or proliferation.
Conclusions:
- Gsα is essential for proper craniofacial development originating from NCCs.
- Gsα plays a critical role in the development of peripheral ganglia derived from NCCs.
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