Loss of coiled-coil protein Cep55 impairs abscission processes and results in p53-dependent apoptosis in developing cortex

Abstract

To produce a brain of normal size and structure, embryonic neural stem cell (NSCs) must tightly regulate their cell divisions. Cerebral cortex NSCs undergo a polarized form of cytokinesis whose regulation is poorly understood. Cytokinetic abscission severs the daughter cells and is mediated by the midbody at the apical membrane. Here we elucidate the role of the coiled-coil midbody protein Cep55 in NSC abscission and brain development. A knockout of Cep55 in mice causes microcephaly with reduced NSCs and neurons, but relatively normal body size. Fixed and live analyses show NSCs lacking Cep55 have decreased but not eliminated ESCRT recruitment, and have abnormal abscission and higher rates of failure. P53-mediated apoptosis is greatly increased in the brain, but not other tissues, and p53 knockout partly rescues brain size. Thus, loss of Cep55 causes abscission defects and failures in multiple cell types, but the secondary p53 response and apoptosis is brain-specific.