Yap and Taz play a crucial role in neural crest-derived craniofacial development

Area of Science:

• Developmental Biology
• Cell Signaling

Background:

• The Hippo signaling pathway's role in cranial neural crest (CNC) development is not well understood.
• Yap and Taz are key downstream effectors of the Hippo pathway.

Purpose of the Study:

• To investigate the function of Yap and Taz in CNC development using conditional knockout mouse models.
• To elucidate the molecular mechanisms by which Yap and Taz regulate CNC development.

Main Methods:

• Conditional ablation of Yap and Taz in CNC using Wnt1(Cre) and Wnt1(Cre2SOR) drivers.
• Analysis of embryonic phenotypes, including vascular development and neural tube closure.
• In vitro studies using O9-1 CNC cells.
• RNA-sequencing and ChIP-PCR to identify target genes and regulatory interactions.

Main Results:

• Yap and Taz deficiency in CNC led to enlarged, hemorrhaging branchial arch blood vessels and hydrocephalus.
• Loss of Yap impaired smooth muscle cell differentiation in CNC cells.
• Yap and Taz regulate Foxc1 expression, a transcription factor implicated in cerebellar development.
• Reduced proliferation in the branchial arch mesenchyme of conditional knockout embryos.
• Yap and Taz directly regulate Foxc1 expression via the Tead transcription factor complex.

Conclusions:

• Yap and Taz are crucial regulators of cranial neural crest cell diversification and development.
• The Hippo pathway, through Yap and Taz, controls vascular integrity and neural tube development.
• Yap/Taz-Tead complex directly regulates Foxc1, linking Hippo signaling to cerebellar development and Dandy-Walker spectrum malformations.