| First Authors |
Elke Gabriel
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| Authors |
Elke Gabriel, Arpit Wason, Anand Ramani, Li Ming Gooi, Patrick Keller, Andrei I. Pozniakovsky, Ina Poser, Florian Noack, Narasimha Swamy Telugu, Federico Calegari, Tomo Šarić, Juergen Hescheler, Anthony Hyman, Marco Gottardo, Giuliano Callaini, Fowzan Sami Alkuraya, Jay Gopalakrishnan
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| Corresponding Authors |
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| Last Authors |
Jay Gopalakrishnan
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| Journal Name |
EMBO journal, The (EMBO J) |
| Volume |
35 |
| Issue |
8 |
| Page Range |
803-819 |
| Open Access |
true |
| Print Publication Date |
2016-04-15 |
| Online Publication Date |
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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 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. |
| PDF |
Gabriel_2016_6460.pdf
(2.3 MB)
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| Cover Image |
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| Affiliated With |
Antibody Facility, Hyman
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| Selected By |
Antibody Facility
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| Acknowledged Services |
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| Publication Status |
Published |
| Edoc Link |
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| Sfx Link |
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| DOI |
10.15252/embj.201593679 |
| PubMed ID |
26929011 |
| WebOfScience Link |
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| Alternative Full Text URL |
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| Display Publisher Download Only |
false |
| Visible On MPI-CBG Website |
true |
| PDF Downloadable |
false |
| Created By |
keller |
| Added Date |
2016-03-15 |
| Last Edited By |
thuem |
| Last Edited Date |
2018-08-15 14:53:11.052 |
| Library ID |
6460 |
| Document ID |
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| Entry Complete |
true |
| eDoc Compliant |
true |
| Include in Edoc Report |
true |
| In Pure |
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| Ready for eDoc Export |
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| Author Affiliations Complete |
false |
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| Project URL |
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| Funding Programme |
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