Microcephaly (an abnormally small cerebral cortex) can be caused by mutations in the gene encoding CDK5RAP2 (cyclin-dependent kinase 5 related activator protein 2). But why do mutations in this centrosomal protein cause microcephaly? To find out, Mark Fleming, Christopher Walsh and colleagues have been studying a mouse model of human microcephaly and now reveal that Cdk5rap2 is essential for cortical progenitor proliferation and survival in mice (see ). They show that the Hertwig's anemia (an) mouse mutant carries a mutation in Cdk5rap2 and exhibits microcephaly that arises from proliferative and survival defects in neuronal progenitors. Cdk5rap2an/an neuronal precursors exit the cell cycle prematurely, they report, and often undergo apoptosis. Finally, they show that these proliferative and survival defects are associated with impaired mitotic progression and with an abnormal mitotic spindle pole number and orientation. The researchers suggest, therefore, that defects in centrosome function and chromosome segregation might underlie the reduction in human brain size caused by mutations in CDK5RAP2.
