The centrosome protein AKNA regulates neurogenesis via microtubule organization

Germán Camargo Ortega, Sven Falk, Pia A. Johansson, Elise Peyre, Loïc Broix, Sanjeeb Kumar Sahu, William Hirst, Thomas Schlichthaerle, Camino Juan Romero, Kalina Draganova, Stanislav Vinopal, Kaviya Chinnappa, Anna Gavranovic, Tugay Karakaya, Thomas Steininger, Juliane Merl-Pham, Regina Feederle, Wei Shao, Song-Hai Shi, Stefanie M. Hauck, Ralf Jungmann, Frank Bradke, Victor Borrell, Arie Geerlof, Simone Reber, Vijay K. Tiwari, Wieland B. Huttner, Michaela Wilsch-Bräuninger, Laurent Nguyen and Magdalena Götz ()
Additional contact information
Germán Camargo Ortega: Helmholtz Center Munich, German Research Center for Environmental Health
Sven Falk: Helmholtz Center Munich, German Research Center for Environmental Health
Pia A. Johansson: Helmholtz Center Munich, German Research Center for Environmental Health
Elise Peyre: University of Liège
Loïc Broix: University of Liège
Sanjeeb Kumar Sahu: Institute of Molecular Biology (IMB)
William Hirst: Humboldt University
Thomas Schlichthaerle: Max Planck Institute of Biochemistry
Camino Juan Romero: Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández
Kalina Draganova: Helmholtz Center Munich, German Research Center for Environmental Health
Stanislav Vinopal: German Center for Neurodegenerative Diseases (DZNE)
Kaviya Chinnappa: Helmholtz Center Munich, German Research Center for Environmental Health
Anna Gavranovic: Helmholtz Center Munich, German Research Center for Environmental Health
Tugay Karakaya: Helmholtz Center Munich, German Research Center for Environmental Health
Thomas Steininger: Helmholtz Center Munich, German Research Center for Environmental Health
Juliane Merl-Pham: Helmholtz Centre Munich, German Research Center for Environmental Health
Regina Feederle: Helmholtz Center Munich, German Research Center for Environmental Health
Wei Shao: Memorial Sloan Kettering Cancer Center
Song-Hai Shi: Memorial Sloan Kettering Cancer Center
Stefanie M. Hauck: Helmholtz Centre Munich, German Research Center for Environmental Health
Ralf Jungmann: Max Planck Institute of Biochemistry
Frank Bradke: German Center for Neurodegenerative Diseases (DZNE)
Victor Borrell: Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández
Arie Geerlof: Institute of Structural Biology, Helmholtz Center Munich, German Research Center for Environmental Health
Simone Reber: Humboldt University
Vijay K. Tiwari: Institute of Molecular Biology (IMB)
Wieland B. Huttner: Max Planck Institute of Molecular Cell Biology and Genetics
Michaela Wilsch-Bräuninger: Max Planck Institute of Molecular Cell Biology and Genetics
Laurent Nguyen: University of Liège
Magdalena Götz: Helmholtz Center Munich, German Research Center for Environmental Health

Nature, 2019, vol. 567, issue 7746, 113-117

Abstract: Abstract The expansion of brain size is accompanied by a relative enlargement of the subventricular zone during development. Epithelial-like neural stem cells divide in the ventricular zone at the ventricles of the embryonic brain, self-renew and generate basal progenitors1 that delaminate and settle in the subventricular zone in enlarged brain regions2. The length of time that cells stay in the subventricular zone is essential for controlling further amplification and fate determination. Here we show that the interphase centrosome protein AKNA has a key role in this process. AKNA localizes at the subdistal appendages of the mother centriole in specific subtypes of neural stem cells, and in almost all basal progenitors. This protein is necessary and sufficient to organize centrosomal microtubules, and promote their nucleation and growth. These features of AKNA are important for mediating the delamination process in the formation of the subventricular zone. Moreover, AKNA regulates the exit from the subventricular zone, which reveals the pivotal role of centrosomal microtubule organization in enabling cells to both enter and remain in the subventricular zone. The epithelial-to-mesenchymal transition is also regulated by AKNA in other epithelial cells, demonstrating its general importance for the control of cell delamination.

Date: 2019
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DOI: 10.1038/s41586-019-0962-4

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