Premium
CPAP promotes timely cilium disassembly to maintain neural progenitor pool
Author(s) -
Gabriel Elke,
Wason Arpit,
Ramani Anand,
Gooi Li Ming,
Keller Patrick,
Pozniakovsky Andrei,
Poser Ina,
Noack Florian,
Telugu Narasimha Swamy,
Calegari Federico,
Šarić Tomo,
Hescheler Jürgen,
Hyman Anthony A,
Gottardo Marco,
Callaini Giuliano,
Alkuraya Fowzan Sami,
Gopalakrishnan Jay
Publication year - 2016
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201593679
Subject(s) - cilium , biology , centrosome , neurogenesis , intraflagellar transport , microbiology and biotechnology , ciliopathies , microcephaly , progenitor cell , progenitor , neuroscience , neural stem cell , stem cell , genetics , cell cycle , cell , phenotype , flagellum , gene
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 ( NPC s) during development. However, mechanisms of NPC s maintenance remain unclear. Here, we report an unexpected role for the cilium in NPC s 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 OFD 1, 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 NPC s. Aberrant CDC function also promotes premature differentiation of NPC s in Seckel iPS ‐derived organoids. Thus, our results suggest a role for cilia in microcephaly and its involvement during neurogenesis and brain size control.