Diverse spinal commissural neuron populations revealed by fate mapping and molecular profiling using a novel Robo3Cre mouse

J Comp Neurol. 2019 Dec 15;527(18):2948-2972. doi: 10.1002/cne.24720. Epub 2019 Jun 14.

Abstract

The two sides of the nervous system coordinate and integrate information via commissural neurons, which project axons across the midline. Commissural neurons in the spinal cord are a highly heterogeneous population of cells with respect to their birthplace, final cell body position, axonal trajectory, and neurotransmitter phenotype. Although commissural axon guidance during development has been studied in great detail, neither the developmental origins nor the mature phenotypes of commissural neurons have been characterized comprehensively, largely due to lack of selective genetic access to these neurons. Here, we generated mice expressing Cre recombinase from the Robo3 locus specifically in commissural neurons. We used Robo3 Cre mice to characterize the transcriptome and various origins of developing commissural neurons, revealing new details about their extensive heterogeneity in molecular makeup and developmental lineage. Further, we followed the fate of commissural neurons into adulthood, thereby elucidating their settling positions and molecular diversity and providing evidence for possible functions in various spinal cord circuits. Our studies establish an important genetic entry point for further analyses of commissural neuron development, connectivity, and function.

Keywords: RRID: AB_10000320; RRID: AB_10000340; RRID: AB_1587626; RRID: AB_2044647; RRID: AB_2068524; RRID: AB_2135660; RRID: AB_2155264; RRID: AB_2155412; RRID: AB_2181865; RRID: AB_2209751; RRID: AB_2278725; RRID: AB_2283049; RRID: AB_2298772; RRID: AB_2301751; RRID: AB_2314897; RRID: AB_2532145; RRID: AB_2565001; RRID: AB_261562; RRID: AB_2619825; RRID: AB_2665452; RRID: AB_476667; RRID: AB_518504; RRID: AB_518614; RRID: AB_528173; RRID: AB_531784; RRID: AB_632234; RRID: AB_732428; Robo3; commissural neurons; gene expression profiling; neurogenesis; spinal cord.

Publication types

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

MeSH terms

  • Animals
  • Chromosome Mapping / methods*
  • Commissural Interneurons / chemistry
  • Commissural Interneurons / metabolism*
  • Female
  • Gene Expression Profiling / methods*
  • Integrases / biosynthesis*
  • Integrases / genetics
  • Male
  • Mice
  • Mice, Transgenic
  • Neurons / chemistry
  • Neurons / metabolism
  • Receptors, Cell Surface / biosynthesis*
  • Receptors, Cell Surface / genetics
  • Spinal Cord / chemistry
  • Spinal Cord / cytology
  • Spinal Cord / metabolism*

Substances

  • Receptors, Cell Surface
  • Robo3 protein, mouse
  • Cre recombinase
  • Integrases