The Kinetochore-Microtubule Coupling Machinery Is Repurposed in Sensory Nervous System Morphogenesis

Dev Cell. 2019 Mar 25;48(6):864-872.e7. doi: 10.1016/j.devcel.2019.02.002. Epub 2019 Feb 28.

Abstract

Dynamic coupling of microtubule ends to kinetochores, built on the centromeres of chromosomes, directs chromosome segregation during cell division. Here, we report that the evolutionarily ancient kinetochore-microtubule coupling machine, the KMN (Knl1/Mis12/Ndc80-complex) network, plays a critical role in neuronal morphogenesis. We show that the KMN network concentrates in microtubule-rich dendrites of developing sensory neurons that collectively extend in a multicellular morphogenetic event that occurs during C. elegans embryogenesis. Post-mitotic degradation of KMN components in sensory neurons disrupts dendritic extension, leading to patterning and functional defects in the sensory nervous system. Structure-guided mutations revealed that the molecular interface that couples kinetochores to spindle microtubules also functions in neuronal development. These results identify a cell-division-independent function for the chromosome-segregation machinery and define a microtubule-coupling-dependent event in sensory nervous system morphogenesis.

Keywords: KMN network; Knl1; Mis12 complex; Ndc80 complex; chromosome segregation; dendrite; kinetochore; microtubule; mitosis; morphogenesis; nervous system; sensory neuron.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans Proteins / metabolism
  • Dendrites / metabolism
  • Embryo, Nonmammalian / metabolism
  • Embryonic Development
  • Kinetochores / metabolism*
  • Microtubules / metabolism*
  • Mitosis
  • Morphogenesis*
  • Nervous System / embryology*
  • Nervous System / metabolism*
  • Sensory Receptor Cells / metabolism*

Substances

  • Caenorhabditis elegans Proteins