TY - JOUR
T1 - The centrosome protein AKNA regulates neurogenesis via microtubule organization
AU - Camargo Ortega, Germán
AU - Falk, Sven
AU - Johansson, Pia A
AU - Peyre, Elise
AU - Broix, Loïc
AU - Sahu, Sanjeeb Kumar
AU - Hirst, William
AU - Schlichthaerle, Thomas
AU - De Juan Romero, Camino
AU - Draganova, Kalina
AU - Vinopal, Stanislav
AU - Chinnappa, Kaviya
AU - Gavranovic, Anna
AU - Karakaya, Tugay
AU - Steininger, Thomas
AU - Merl-Pham, Juliane
AU - Feederle, Regina
AU - Shao, Wei
AU - Shi, Song-Hai
AU - Hauck, Stefanie M
AU - Jungmann, Ralf
AU - Bradke, Frank
AU - Borrell, Victor
AU - Geerlof, Arie
AU - Reber, Simone
AU - Tiwari, Vijay K
AU - Huttner, Wieland B
AU - Wilsch-Bräuninger, Michaela
AU - Nguyen, Laurent
AU - Götz, Magdalena
PY - 2019/3
Y1 - 2019/3
N2 - 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.
AB - 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.
KW - Animals
KW - Cell Movement
KW - Cells, Cultured
KW - Centrosome/metabolism
KW - DNA-Binding Proteins/metabolism
KW - Epithelial Cells/metabolism
KW - Epithelial-Mesenchymal Transition
KW - Humans
KW - Intercellular Junctions/metabolism
KW - Interphase
KW - Lateral Ventricles/anatomy & histology
KW - Mammary Glands, Animal/cytology
KW - Mice
KW - Microtubules/metabolism
KW - Neurogenesis
KW - Nuclear Proteins/metabolism
KW - Organ Size
KW - Organoids/cytology
KW - Transcription Factors/metabolism
U2 - 10.1038/s41586-019-0962-4
DO - 10.1038/s41586-019-0962-4
M3 - Journal article
C2 - 30787442
SN - 0028-0836
VL - 567
SP - 113
EP - 117
JO - Nature
JF - Nature
IS - 7746
ER -