Abstract
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.
Highlights
During corticogenesis, excitatory neurons of the mammalian neocortex originate from proliferative radial glial cells (RGCs) extending fibers to the pial surface[1]
Our study identifies an important function for the microtubule-severing protein p60 katanin in embryonic survival, and highlights its role in neuronal progenitor proliferation in the developing cortex and during adult hippocampal neurogenesis
To investigate whether katanin p60 haploinsufficiency affects neuronal progenitors in adulthood, we focused our analysis on adult hippocampal neurogenesis
Summary
Excitatory neurons of the mammalian neocortex originate from proliferative radial glial cells (RGCs) extending fibers to the pial surface[1]. Upon activation, they self-renew and generate intermediate neuronal progenitors (NPCs) that subsequently differentiate into neuroblasts, dentate granule cells (DGCs) and astrocytes[8,9]. Our study identifies an important function for the microtubule-severing protein p60 katanin in embryonic survival, and highlights its role in neuronal progenitor proliferation in the developing cortex and during adult hippocampal neurogenesis
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