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Journal Article

CPAP promotes timely cilium disassembly to maintain neural progenitor pool.

MPS-Authors
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Keller,  Patrick
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

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Pozniakovsky,  Andrei I.
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

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Poser,  Ina
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

Noack,  Florian
Max Planck Society;

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Hyman,  Anthony
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

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Citation

Gabriel, E., Wason, A., Ramani, A., Gooi, L. M., Keller, P., Pozniakovsky, A. I., et al. (2016). CPAP promotes timely cilium disassembly to maintain neural progenitor pool. The EMBO Journal, 35(8), 803-819.


Cite as: https://hdl.handle.net/21.11116/0000-0001-02B3-2
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 ofNPCs maintenance remain unclear. Here, we report an unexpected role for the cilium inNPCs maintenance and identifyCPAPas a negative regulator of ciliary length independent of its role in centrosome biogenesis. At the onset of cilium disassembly,CPAPprovides a scaffold for the cilium disassembly complex (CDC), which includes Nde1, Aurora A, andOFD1, recruited to the ciliary base for timely cilium disassembly. In contrast, mutatedCPAPfails to localize at the ciliary base associated with inefficientCDCrecruitment, long cilia, retarded cilium disassembly, and delayed cell cycle re-entry leading to premature differentiation of patientiPS-derivedNPCs. AberrantCDCfunction also promotes premature differentiation ofNPCs in SeckeliPS-derived organoids. Thus, our results suggest a role for cilia in microcephaly and its involvement during neurogenesis and brain size control.