Prolonged Mitosis of Neural Progenitors Alters Cell Fate in the Developing Brain.

Journal Article

Embryonic neocortical development depends on balanced production of progenitors and neurons. Genetic mutations disrupting progenitor mitosis frequently impair neurogenesis; however, the link between altered mitosis and cell fate remains poorly understood. Here we demonstrate that prolonged mitosis of radial glial progenitors directly alters neuronal fate specification and progeny viability. Live imaging of progenitors from a neurogenesis mutant, Magoh(+/-), reveals that mitotic delay significantly correlates with preferential production of neurons instead of progenitors, as well as apoptotic progeny. Independently, two pharmacological approaches reveal a causal relationship between mitotic delay and progeny fate. As mitotic duration increases, progenitors produce substantially more apoptotic progeny or neurons. We show that apoptosis, but not differentiation, is p53 dependent, demonstrating that these are distinct outcomes of mitotic delay. Together our findings reveal that prolonged mitosis is sufficient to alter fates of radial glia progeny and define a new paradigm to understand how mitosis perturbations underlie brain size disorders such as microcephaly.

Full Text

Duke Authors

Cited Authors

  • Pilaz, L-J; McMahon, JJ; Miller, EE; Lennox, AL; Suzuki, A; Salmon, E; Silver, DL

Published Date

  • January 2016

Published In

Volume / Issue

  • 89 / 1

Start / End Page

  • 83 - 99

PubMed ID

  • 26748089

Electronic International Standard Serial Number (EISSN)

  • 1097-4199

International Standard Serial Number (ISSN)

  • 0896-6273

Digital Object Identifier (DOI)

  • 10.1016/j.neuron.2015.12.007

Language

  • eng