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Nature. 2019 Mar;567(7746):113-117. doi: 10.1038/s41586-019-0962-4. Epub 2019 Feb 20.

The centrosome protein AKNA regulates neurogenesis via microtubule organization.

Author information

1
Institute of Stem Cell Research, Helmholtz Center Munich, German Research Center for Environmental Health, Munich, Germany.
2
Physiological Genomics, Biomedical Center, Ludwig-Maximilians University, Munich, Germany.
3
Graduate School of Systemic Neurosciences, Biocenter, Ludwig-Maximilians University, Munich, Germany.
4
Laboratory of Molecular Neurogenetics, Lund University, Lund, Sweden.
5
GIGA-Stem Cells, Molecular regulation of neurogenesis, University of Liège, Liège, Belgium.
6
Institute of Molecular Biology (IMB), Mainz, Germany.
7
IRI for the Life Sciences, Humboldt University, Berlin, Germany.
8
Research School of Biology, The Australian National University, Canberra, Australian Capital Territory, Australia.
9
Max Planck Institute of Biochemistry, Martinsried, Germany.
10
Department of Physics and Center for Nanoscience, Ludwig Maximilians University, Munich, Germany.
11
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández, Sant Joan d'Alacant, Spain.
12
Laboratory for Axon Growth and Regeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
13
Research Unit Protein Science, Helmholtz Centre Munich, German Research Center for Environmental Health, Munich, Germany.
14
Institute for Diabetes and Obesity, Monoclonal Antibody Core Facility, Helmholtz Center Munich, German Research Center for Environmental Health, Munich, Germany.
15
SYNERGY, Excellence Cluster of Systems Neurology, Biomedical Center, Ludwig-Maximilians University, Munich, Germany.
16
Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
17
BCMB Allied Graduate Program, Weill Cornell Medical College, New York, NY, USA.
18
Protein Expression and Purification Facility, Institute of Structural Biology, Helmholtz Center Munich, German Research Center for Environmental Health, Munich, Germany.
19
University of Applied Sciences, Berlin, Germany.
20
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
21
Institute of Stem Cell Research, Helmholtz Center Munich, German Research Center for Environmental Health, Munich, Germany. magdalena.goetz@helmholtz-muenchen.de.
22
Physiological Genomics, Biomedical Center, Ludwig-Maximilians University, Munich, Germany. magdalena.goetz@helmholtz-muenchen.de.
23
Max Planck Institute of Biochemistry, Martinsried, Germany. magdalena.goetz@helmholtz-muenchen.de.
24
SYNERGY, Excellence Cluster of Systems Neurology, Biomedical Center, Ludwig-Maximilians University, Munich, Germany. magdalena.goetz@helmholtz-muenchen.de.

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.

PMID:
30787442
DOI:
10.1038/s41586-019-0962-4

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