Thyroid bud morphogenesis requires CDC42- and SHROOM3-dependent apical constriction

Area of Science:

• Developmental Biology
• Cell Biology
• Genetics

Background:

• Epithelial morphogenesis during early organogenesis involves dynamic changes in cell shape and polarity.
• Rho GTPases, including Cdc42, are critical regulators of these cellular processes.
• The specific roles of Cdc42 in foregut development and organ bud formation remain incompletely understood.

Purpose of the Study:

• To investigate the function of Cdc42 in mouse foregut development and the formation of embryonic organ buds.
• To determine the impact of Cdc42 ablation on epithelial cell polarity, morphology, and organogenesis.
• To explore the potential involvement of SHROOM3 in Cdc42-mediated apical constriction.

Main Methods:

• Conditional ablation of Cdc42 in mouse embryos post-gastrulation.
• Analysis of epithelial cell polarity, morphology, and viability in the ventral pharyngeal endoderm.
• Assessment of liver, lung, and thyroid bud outgrowth and morphology.
• Examination of SHROOM3 expression and localization in wild-type and Cdc42-deficient embryos.
• Analysis of Shroom3 gene trap mutant embryos.

Main Results:

• Cdc42 deficiency led to loss of apical-basal polarity and columnar epithelial morphology in the ventral pharyngeal endoderm.
• Cell viability was impaired, but proliferation was unaffected in the foregut endoderm of Cdc42-deficient embryos.
• Outgrowth of liver, lung, and thyroid buds was severely reduced; thyroid bud apical constriction was absent.
• SHROOM3 localization was disrupted in Cdc42-deficient embryos, and Shroom3 mutants also lacked thyroid bud apical constriction.

Conclusions:

• Cdc42 is indispensable for maintaining epithelial polarity and organization in the developing foregut endoderm.
• Cdc42 plays a crucial role in apical constriction during thyroid bud formation, potentially via SHROOM3.
• These findings highlight Cdc42's importance in regulating epithelial morphogenesis for successful organogenesis.