Talpid3-binding centrosomal protein Cep120 is required for centriole duplication and proliferation of cerebellar granule neuron progenitors.

Publication TypeJournal Article
Year of Publication2014
AuthorsWu C, Yang M, Li J, Wang C, Cao T, Tao K, Wang B
JournalPLoS One
Date Published2014
KeywordsAnimals, Cell Cycle Proteins, Cell Proliferation, Cells, Cultured, Centrioles, Cerebellum, Developmental Disabilities, Female, Gene Deletion, Hydrocephalus, Male, Mice, Mice, Inbred C57BL, Nervous System Malformations, Neural Stem Cells, Protein Interaction Maps, Signal Transduction

Granule neuron progenitors (GNPs) are the most abundant neuronal type in the cerebellum. GNP proliferation and thus cerebellar development require Sonic hedgehog (Shh) secreted from Purkinje cells. Shh signaling occurs in primary cilia originating from the mother centriole. Centrioles replicate only once during a typical cell cycle and are responsible for mitotic spindle assembly and organization. Recent studies have linked cilia function to cerebellar morphogenesis, but the role of centriole duplication in cerebellar development is not known. Here we show that centrosomal protein Cep120 is asymmetrically localized to the daughter centriole through its interaction with Talpid3 (Ta3), another centrosomal protein. Cep120 null mutant mice die in early gestation with abnormal heart looping. Inactivation of Cep120 in the central nervous system leads to both hydrocephalus, due to the loss of cilia on ependymal cells, and severe cerebellar hypoplasia, due to the failed proliferation of GNPs. The mutant GNPs lack Hedgehog pathway activity. Cell biological studies show that the loss of Cep120 results in failed centriole duplication and consequently ciliogenesis, which together underlie Cep120 mutant cerebellar hypoplasia. Thus, our study for the first time links a centrosomal protein necessary for centriole duplication to cerebellar morphogenesis.

Alternate JournalPLoS ONE
PubMed ID25251415
PubMed Central IDPMC4176001
Grant ListR01CA111673 / CA / NCI NIH HHS / United States
R01GM070820 / GM / NIGMS NIH HHS / United States