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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: MPI-CBG Publications 2016 (archival)     Display Documents



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ID: 732427.0, MPI für molekulare Zellbiologie und Genetik / MPI-CBG Publications 2016 (archival)
CPAP promotes timely cilium disassembly to maintain neural progenitor pool.
Authors:Gabriel, Elke; Wason, Arpit; Ramani, Anand; Gooi, Li Ming; Keller, Patrick; Pozniakovsky, Andrei I.; Poser, Ina; Noack, Florian; Telugu, Narasimha Swamy; Calegari, Federico; Šarić, Tomo; Hescheler, Juergen; Hyman, Anthony; Gottardo, Marco; Callaini, Giuliano; Alkuraya, Fowzan Sami; Gopalakrishnan, Jay
Date of Publication (YYYY-MM-DD):2016
Title of Journal:The EMBO Journal
Volume:35
Issue / Number:8
Start Page:803
End Page:819
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description: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.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:Thüm
Affiliations:MPI für molekulare Zellbiologie und Genetik
Identifiers:LOCALID:6460
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