Roles of developmentally regulated KIF2A alternative isoforms in cortical neuron migration and differentiation

Development. 2021 Feb 22;148(4):dev192674. doi: 10.1242/dev.192674.


KIF2A is a kinesin motor protein with essential roles in neural progenitor division and axonal pruning during brain development. However, how different KIF2A alternative isoforms function during development of the cerebral cortex is not known. Here, we focus on three Kif2a isoforms expressed in the developing cortex. We show that Kif2a is essential for dendritic arborization in mice and that the functions of all three isoforms are sufficient for this process. Interestingly, only two of the isoforms can sustain radial migration of cortical neurons; a third isoform, lacking a key N-terminal region, is ineffective. By proximity-based interactome mapping for individual isoforms, we identify previously known KIF2A interactors, proteins localized to the mitotic spindle poles and, unexpectedly, also translation factors, ribonucleoproteins and proteins that are targeted to organelles, prominently to the mitochondria. In addition, we show that a KIF2A mutation, which causes brain malformations in humans, has extensive changes to its proximity-based interactome, with depletion of mitochondrial proteins identified in the wild-type KIF2A interactome. Our data raises new insights about the importance of alternative splice variants during brain development.

Keywords: Alternative splicing; Cortical development; KIF2A; Proximity-interactome mapping.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Animals
  • Cell Differentiation / genetics*
  • Cell Movement / genetics*
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Kinesins / genetics*
  • Kinesins / metabolism
  • Mice
  • Mutation
  • Neurogenesis / genetics
  • Neurons / cytology*
  • Neurons / metabolism*
  • Proteomics / methods
  • RNA Isoforms
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism


  • RNA Isoforms
  • Repressor Proteins
  • KIF2A protein, mouse
  • Kinesins