Inter-axonal molecular crosstalk via Lumican proteoglycan sculpts murine cervical corticospinal innervation by distinct subpopulations. Academic Article uri icon

Overview

abstract

  • How CNS circuits sculpt their axonal arbors into spatially and functionally organized domains is not well understood. Segmental specificity of corticospinal connectivity is an exemplar for such regional specificity of many axon projections. Corticospinal neurons (CSN) innervate spinal and brainstem targets with segmental precision, controlling voluntary movement. Multiple molecularly distinct CSN subpopulations innervate the cervical cord for evolutionarily enhanced precision of forelimb movement. Evolutionarily newer CSNBC-lat exclusively innervate bulbar-cervical targets, while CSNmedial are heterogeneous; distinct subpopulations extend axons to either bulbar-cervical or thoraco-lumbar segments. We identify that Lumican controls balance of cervical innervation between CSNBC-lat and CSNmedial axons during development, which is maintained into maturity. Lumican, an extracellular proteoglycan expressed by CSNBC-lat, non-cell-autonomously suppresses cervical collateralization by multiple CSNmedial subpopulations. This inter-axonal molecular crosstalk between CSN subpopulations controls murine corticospinal circuitry refinement and forelimb dexterity. Such crosstalk is generalizable beyond the corticospinal system for evolutionary incorporation of new neuron populations into preexisting circuitry.

publication date

  • March 17, 2023

Research

keywords

  • Axons
  • Spinal Cord

Identity

Scopus Document Identifier

  • 85150339869

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2023.112182

PubMed ID

  • 36934325

Additional Document Info

volume

  • 42

issue

  • 3