CPAP promotes timely cilium disassembly to maintain neural progenitor pool

• Elke Gabriel ^[1] ; Arpit Wason ^[1] ; Anand Ramani ^[1] ; Li Ming Gooi ^[1] ; Patrick Keller ^[2] ; Andrei Pozniakovsky ^[2] ; Ina Poser ^[2] ; Florian Noack ^[4] ; Narasimha Swamy Telugu ^[1] ; Federico Calegari ^[4] ; Tomo Šarić ^[1] ; Jürgen Hescheler ^[1] ; Anthony A Hyman ^[2] ; Marco Gottardo ^[3] ; Giuliano Callaini ^[3] ; Fowzan Sami Alkuraya ^[5] ; Jay Gopalakrishnan ^[1]
  1. [1] University of Cologne

     University of Cologne

     Kreisfreie Stadt Köln, Alemania

     
  2. [2] Max Planck Institute of Molecular Cell Biology and Genetics

     Max Planck Institute of Molecular Cell Biology and Genetics

     Kreisfreie Stadt Dresden, Alemania

     
  3. [3] Università degli Studi di Siena

     Università degli Studi di Siena

     Siena, Italia

     
  4. [4] 3 DFG‐Research Center and Cluster of Excellence for Regenerative Therapies TU‐Dresden Dresden Germany
  5. [5] 6 Department of Genetics King Faisal Specialist Hospital and Research Center Alfasial University Riyadh Saudi Arabia; 7 Department of Anatomy and Cell Biology College of Medicine Alfasial University Riyadh Saudi Arabia

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 35, Nº. 8, 2016, págs. 803-819
• Idioma: inglés
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  • 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.