Katanin p80 regulates human cortical development by limiting centriole and cilia number

Neuron. 2014 Dec 17;84(6):1240-57. doi: 10.1016/j.neuron.2014.12.017.


Katanin is a microtubule-severing complex whose catalytic activities are well characterized, but whose in vivo functions are incompletely understood. Human mutations in KATNB1, which encodes the noncatalytic regulatory p80 subunit of katanin, cause severe microlissencephaly. Loss of Katnb1 in mice confirms essential roles in neurogenesis and cell survival, while loss of zebrafish katnb1 reveals specific roles for katnin p80 in early and late developmental stages. Surprisingly, Katnb1 null mutant mouse embryos display hallmarks of aberrant Sonic hedgehog signaling, including holoprosencephaly. KATNB1-deficient human cells show defective proliferation and spindle structure, while Katnb1 null fibroblasts also demonstrate a remarkable excess of centrioles, with supernumerary cilia but deficient Hedgehog signaling. Our results reveal unexpected functions for KATNB1 in regulating overall centriole, mother centriole, and cilia number, and as an essential gene for normal Hedgehog signaling during neocortical development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / physiology*
  • Animals
  • Case-Control Studies
  • Cell Proliferation / genetics
  • Cell Proliferation / physiology
  • Centrioles / genetics
  • Centrioles / physiology*
  • Cerebral Cortex / abnormalities
  • Cerebral Cortex / cytology*
  • Cerebral Cortex / embryology*
  • Cerebral Cortex / metabolism
  • Cilia / genetics
  • Cilia / physiology*
  • Embryo, Mammalian
  • Embryonic Development / genetics
  • European Continental Ancestry Group / genetics
  • Fibroblasts / metabolism
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism
  • Humans
  • Katanin
  • Mice
  • Microcephaly / genetics
  • Mutation
  • Pedigree
  • RNA Splicing / genetics
  • Zebrafish


  • Hedgehog Proteins
  • Shh protein, mouse
  • Adenosine Triphosphatases
  • Katanin