Universität zu Köln

Gabriel, Elke, Wason, Arpit, Ramani, Anand, Gooi, Li Ming, Keller, Patrick, Pozniakovsky, Andrei, Poser, Ina, Noack, Florian, Telugu, Narasimha Swamy, Calegari, Federico, Saric, Tomo ORCID: 0000-0001-8344-1095, Hescheler, Juergen, Hyman, Anthony A., Gottardo, Marco ORCID: 0000-0001-8649-7799, Callaini, Giuliano ORCID: 0000-0003-2252-0309, Alkuraya, Fowzan Sami and Gopalakrishnan, Jay (2016). CPAP promotes timely cilium disassembly to maintain neural progenitor pool. Embo J., 35 (8). S. 803 - 820. HOBOKEN: WILEY-BLACKWELL. ISSN 1460-2075

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gabriel, Elke UNSPECIFIED UNSPECIFIED UNSPECIFIED Wason, Arpit UNSPECIFIED UNSPECIFIED UNSPECIFIED Ramani, Anand UNSPECIFIED UNSPECIFIED UNSPECIFIED Gooi, Li Ming UNSPECIFIED UNSPECIFIED UNSPECIFIED Keller, Patrick UNSPECIFIED UNSPECIFIED UNSPECIFIED Pozniakovsky, Andrei UNSPECIFIED UNSPECIFIED UNSPECIFIED Poser, Ina UNSPECIFIED UNSPECIFIED UNSPECIFIED Noack, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Telugu, Narasimha Swamy UNSPECIFIED UNSPECIFIED UNSPECIFIED Calegari, Federico UNSPECIFIED UNSPECIFIED UNSPECIFIED Saric, Tomo UNSPECIFIED orcid.org/0000-0001-8344-1095 UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Hyman, Anthony A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gottardo, Marco UNSPECIFIED orcid.org/0000-0001-8649-7799 UNSPECIFIED Callaini, Giuliano UNSPECIFIED orcid.org/0000-0003-2252-0309 UNSPECIFIED Alkuraya, Fowzan Sami UNSPECIFIED UNSPECIFIED UNSPECIFIED Gopalakrishnan, Jay UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-278599
DOI:	10.15252/embj.201593679
Journal or Publication Title:	Embo J.
Volume:	35
Number:	8
Page Range:	S. 803 - 820
Date:	2016
Publisher:	WILEY-BLACKWELL
Place of Publication:	HOBOKEN
ISSN:	1460-2075
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CILIARY TRANSITION ZONE; CELL-CYCLE; BRAIN-DEVELOPMENT; SECKEL SYNDROME; STEM-CELLS; CENTRIOLE; CILIOGENESIS; CENTROSOME; PROTEIN; NEUROGENESIS Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27859