CROCCP2 acts as a human-specific modifier of cilia dynamics and mTOR signalling to promote expansion of cortical progenitors.
van Heurck, R.; Wojno, M.; Suzuki, I.; Velez, F.; Bonnefont, J.; Erkol, E.; Nguyen, D. T.; Herpoel, A.; Bilheu, A.; Ledent, C.; Vanderhaeghen, P.
Show abstract
The primary cilum is a central component of signalling during neural development, from regional patterning to neuronal differentiation. Here we focus on CROCCP2, a hominid-specific gene duplicate from CROCC (Ciliary Rootlet Coiled Coil), also known as rootletin, that encodes the major protein component of the ciliary rootlet. We find that CROCCP2 is highly expressed in the human fetal brain and not in other primate species. CROCCP2 gain of function in the mouse embryonic cortex results in decreased ciliogenesis, increased mTOR signalling, and increased cell size of radial glial cells, leading to increased generation of intermediate/basal progenitors and increased neuronal output. CROCCP2 impacts cilia dynamics and neurogenesis by inhibition of the IFT20 ciliary trafficking protein. Our data identify a human-specific protein that drives cortical basal progenitor expansion through modulation of ciliary dynamics.
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