Plexin-B2 controls the timing of differentiation and the motility of cerebellar granule neurons

Elife. 2021 Jun 8:10:e60554. doi: 10.7554/eLife.60554.

Abstract

Plexin-B2 deletion leads to aberrant lamination of cerebellar granule neurons (CGNs) and Purkinje cells. Although in the cerebellum Plexin-B2 is only expressed by proliferating CGN precursors in the outer external granule layer (oEGL), its function in CGN development is still elusive. Here, we used 3D imaging, in vivo electroporation and live-imaging techniques to study CGN development in novel cerebellum-specific Plxnb2 conditional knockout mice. We show that proliferating CGNs in Plxnb2 mutants not only escape the oEGL and mix with newborn postmitotic CGNs. Furthermore, motility of mitotic precursors and early postmitotic CGNs is altered. Together, this leads to the formation of ectopic patches of CGNs at the cerebellar surface and an intermingling of normally time-stamped parallel fibers in the molecular layer (ML), and aberrant arborization of Purkinje cell dendrites. There results suggest that Plexin-B2 restricts CGN motility and might have a function in cytokinesis.

Keywords: cell migration; cerebellum; cytokinesis; developmental biology; mouse; neuroscience; semaphorins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cerebellum / cytology*
  • Female
  • Male
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins* / genetics
  • Nerve Tissue Proteins* / metabolism
  • Neurons* / cytology
  • Neurons* / metabolism
  • Neurons* / physiology

Substances

  • Nerve Tissue Proteins
  • Plxnb2 protein, mouse

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.