CPAP promotes timely cilium disassembly to maintain neural progenitor pool
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
A mutation in the centrosomal-P4.1-associated protein (CPAP) causes Seckel syndrome with microcephaly, which is suggested to arise from a decline in neural progenitor cells (NPCs) during development. However, mechanisms of NPCs maintenance remain unclear. Here, we report an unexpected role for the cilium in NPCs maintenance and identify CPAP as a negative regulator of ciliary length independent of its role in centrosome biogenesis. At the onset of cilium disassembly, CPAP provides a scaffold for the cilium disassembly complex (CDC), which includes Nde1, Aurora A, and OFD1, recruited to the ciliary base for timely cilium disassembly. In contrast, mutated CPAP fails to localize at the ciliary base associated with inefficient CDC recruitment, long cilia, retarded cilium disassembly, and delayed cell cycle re-entry leading to premature differentiation of patient iPS-derived NPCs. Aberrant CDC function also promotes premature differentiation of NPCs in Seckel iPS-derived organoids. Thus, our results suggest a role for cilia in microcephaly and its involvement during neurogenesis and brain size control.
Details
Original language | English |
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Pages (from-to) | 803-819 |
Number of pages | 17 |
Journal | EMBO Journal |
Volume | 35 |
Issue number | 8 |
Publication status | Published - 15 Apr 2016 |
Peer-reviewed | Yes |
External IDs
PubMed | 26929011 |
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Keywords
ASJC Scopus subject areas
Keywords
- brain organoids, cilium, CPAP, microcephaly, neural progenitor cell maintenance