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

Dhanya K. Cheerambathur, Bram Prevo, Tiffany Lynn Chow, Neil Hattersley, Shaohe Wang, Zhiling Zhao, Taekyung Kim, Adina Gerson-Gurwitz, Karen Oegema, Rebecca Green, Arshad Desai

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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.

Original languageEnglish
Pages (from-to)864-872.e7
JournalDevelopmental Cell
Volume48
Issue number6
DOIs
StatePublished - 25 Mar 2019
Externally publishedYes

Keywords

  • KMN network
  • Knl1
  • Mis12 complex
  • Ndc80 complex
  • chromosome segregation
  • dendrite
  • kinetochore
  • microtubule
  • mitosis
  • morphogenesis
  • nervous system
  • sensory neuron

ASJC Scopus subject areas

  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • Developmental Biology
  • Cell Biology

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