Centrosome anchoring regulates progenitor properties and cortical formation

Area of Science:

• Neuroscience
• Developmental Biology
• Cell Biology

Background:

• Radial glial progenitor cells (RGPs) are crucial for generating neurons and glia in the developing mammalian cerebral cortex.
• The apical positioning of the centrosome in RGPs is a unique subcellular organization with an unknown molecular basis and function.

Purpose of the Study:

• To investigate the molecular mechanisms and functional significance of centrosome anchoring to the apical membrane in cortical RGPs.
• To elucidate the role of centrosome organization in regulating RGP behavior and cerebral cortex development.

Main Methods:

• Utilized mouse models to study the function of centrosomal protein 83 (CEP83).
• Investigated the effects of CEP83 removal on centrosome anchoring, cell mechanics, and RGP proliferation.
• Assessed the involvement of the YAP signaling pathway in response to altered centrosome organization.

Main Results:

• CEP83 is essential for forming distal appendages that anchor the mother centriole to the apical membrane in RGPs.
• Removal of CEP83 disrupts centrosome anchorage, leading to microtubule disorganization and altered apical membrane mechanics.
• CEP83 depletion activates YAP signaling, causing excessive RGP proliferation, increased intermediate progenitor cells, and enlarged, abnormally folded cortex.
• Simultaneous elimination of YAP rescues the cortical enlargement and folding defects induced by CEP83 removal.

Conclusions:

• Centrosome anchoring to the apical membrane is critical for regulating the mechanical properties of cortical RGPs.
• This mechanical regulation influences RGP mitotic behavior, progenitor cell production, and ultimately, the size and intricate folding of the mammalian cerebral cortex.
• Reveals a novel role for the centrosome in mechanotransduction pathways governing neural progenitor cell behavior and brain development.