CCRB Seminar: Dr Parthiv Haldipur

Centre for Craniofacial & Regenerative Biology Seminar

“Human specific developmental programsprovide clues on the mechanisms ofcerebellar disease pathogenesis”

Dr Parthiv Haldipur, Seattle Children’s Research Institute, University of Washington

Thursday 6th June 2019 at 12.00

Lecture Room, Floor 18, Tower Wing

 

Cerebellar development has been well studied in animal models.However, little is known about the cellular and molecular events driving human cerebellum development. Our analysis of the histological and molecular landscape of the developing human cerebellum from 30 postconception days to 9 postnatal months reveals significant differences in developmental patterns between human and mouse, including the spatiotemporal expansion of primary progenitor zones. Particularly striking is the prolonged presence of the rhombic lip (RL); a region that gives rise to all glutamatergic neurons in the cerebellum, including granule cell precursors (GCPs) which differentiate into granule neurons and account for 80% of all neurons in the entire adult brain. The human rhombic lip also undergoes multiple morphological changes which culminate in the formation of a progenitor pool in the posterior vermis,with no equivalent in any model organism, including the macaque. Wealso find disruptions in human rhombic lip development are associated with cerebellar hypoplasia and Dandy-Walker malformation. Since most of our interpretation of development and disease is based onresults obtained using animal models, this new data fundamentally alters the current paradigms of human cerebellar disease mechanisms.