Genetic Labeling of Nuclei-Specific Thalamocortical Neurons Reveals Putative Sensory-Modality Specific Genes

Cereb Cortex. 2017 Nov 1;27(11):5054-5069. doi: 10.1093/cercor/bhw290.

Abstract

The thalamus is a central brain structure with topographically ordered long-range axonal projections that convey sensory information to the cortex via distinct nuclei. Although there is an increasing knowledge about genes important for thalamocortical (TC) development, the identification of genetic landmarks of the distinct thalamic nuclei during the embryonic development has not been addressed systematically. Indeed, a more comprehensive understanding of how the axons from the individual nuclei find their way and connect to their corresponding cortical area is called for. Here, we used a genetic dual labeling strategy in mice to purify distinct principal sensory thalamic neurons. Subsequent genome-wide transcriptome profiling revealed genes specifically expressed in each nucleus during embryonic development. Analysis of regulatory regions of the identified genes revealed key transcription factors and networks that likely underlie the specification of individual sensory-modality TC connections. Finally, the importance of correct axon targeting for the specific sensory-modality population transcriptome was evidenced in a Sema6A mutant, in which visual TC axons are derailed at embryonic life. In sum, our data determined the developmental transcriptional profile of the TC neurons that will eventually support sensory processing.

Keywords: brain development; gene expression; regional patterning; sensory system; thalamus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Cerebral Cortex / cytology*
  • Cerebral Cortex / embryology*
  • Cerebral Cortex / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Mice, Transgenic
  • Mutation
  • Neural Pathways / cytology
  • Neural Pathways / embryology
  • Neural Pathways / metabolism
  • Semaphorins / deficiency
  • Semaphorins / genetics
  • Sensory Receptor Cells / cytology*
  • Sensory Receptor Cells / metabolism*
  • Thalamic Nuclei / cytology*
  • Thalamic Nuclei / embryology*
  • Thalamic Nuclei / metabolism
  • Transcriptome

Substances

  • Gbx2 protein, mouse
  • Homeodomain Proteins
  • Sema6a protein, mouse
  • Semaphorins