TY - JOUR
T1 - The Microtubule Severing Protein Katanin Regulates Proliferation of Neuronal Progenitors in Embryonic and Adult Neurogenesis
AU - Lombino, Franco L.
AU - Muhia, Mary
AU - Lopez-Rojas, Jeffrey
AU - Brill, Monika S.
AU - Thies, Edda
AU - Ruschkies, Laura
AU - Lutz, David
AU - Richter, Melanie
AU - Hausrat, Torben J.
AU - Lopes, André T.
AU - McNally, Francis J.
AU - Hermans-Borgmeyer, Irm
AU - Dunleavy, Jessica E.M.
AU - Hoffmeister-Ullerich, Sabine
AU - Frotscher, Michael
AU - Misgeld, Thomas
AU - Kreutz, Michael R.
AU - de Anda, Froylan Calderon
AU - Kneussel, Matthias
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Microtubule severing regulates cytoskeletal rearrangement underlying various cellular functions. Katanin, a heterodimer, consisting of catalytic (p60) and regulatory (p80) subunits severs dynamic microtubules to modulate several stages of cell division. The role of p60 katanin in the mammalian brain with respect to embryonic and adult neurogenesis is poorly understood. Here, we generated a Katna1 knockout mouse and found that consistent with a critical role of katanin in mitosis, constitutive homozygous Katna1 depletion is lethal. Katanin p60 haploinsufficiency induced an accumulation of neuronal progenitors in the subventricular zone during corticogenesis, and impaired their proliferation in the adult hippocampus dentate gyrus (DG) subgranular zone. This did not compromise DG plasticity or spatial and contextual learning and memory tasks employed in our study, consistent with the interpretation that adult neurogenesis may be associated with selective forms of hippocampal-dependent cognitive processes. Our data identify a critical role for the microtubule-severing protein katanin p60 in regulating neuronal progenitor proliferation in vivo during embryonic development and adult neurogenesis.
AB - Microtubule severing regulates cytoskeletal rearrangement underlying various cellular functions. Katanin, a heterodimer, consisting of catalytic (p60) and regulatory (p80) subunits severs dynamic microtubules to modulate several stages of cell division. The role of p60 katanin in the mammalian brain with respect to embryonic and adult neurogenesis is poorly understood. Here, we generated a Katna1 knockout mouse and found that consistent with a critical role of katanin in mitosis, constitutive homozygous Katna1 depletion is lethal. Katanin p60 haploinsufficiency induced an accumulation of neuronal progenitors in the subventricular zone during corticogenesis, and impaired their proliferation in the adult hippocampus dentate gyrus (DG) subgranular zone. This did not compromise DG plasticity or spatial and contextual learning and memory tasks employed in our study, consistent with the interpretation that adult neurogenesis may be associated with selective forms of hippocampal-dependent cognitive processes. Our data identify a critical role for the microtubule-severing protein katanin p60 in regulating neuronal progenitor proliferation in vivo during embryonic development and adult neurogenesis.
UR - http://www.scopus.com/inward/record.url?scp=85074355126&partnerID=8YFLogxK
U2 - 10.1038/s41598-019-52367-3
DO - 10.1038/s41598-019-52367-3
M3 - Article
C2 - 31685876
AN - SCOPUS:85074355126
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 15940
ER -