Primary microcephaly, a human developmental disorder characterized by a small brain, can be caused by mutations in microcephalin (MCPH1) – a protein involved in the timing of chromosome condensation and in DNA repair. Two papers in this issue of JCS show how researchers are now turning to flies to study the developmental roles of MCPH1. On , Andrew Jackson and co-authors report that the Drosophila ortholog coordinates the centrosomal and nuclear mitotic cycles in syncitial fly embryos. MCPH1 localizes with DNA during interphase, they report, but a short isoform relocalizes to the centrosome and spindle during mitosis, and is required for the syncitial nuclear divisions that occur in early fly embryos. Like Jackson's team, Laura Lee and co-authors report that embryos of mcph1-null female flies undergo mitotic arrest (see ). They show that this arrest follows activation of the checkpoint kinase Chk2 and propose a model in which lack of mcph1 results in mitotic entry with unreplicated DNA and genomic instability. Finally, Lee and colleagues report that mcph1 is required for formation of normal brain structures in adult male flies. Together, these two papers suggest that studies in fly embryos could help to unravel how MCPH1 determines human brain size.
