Combinatorial expression of Brn3 transcription factors in somatosensory neurons: genetic and morphologic analysis

J Neurosci. 2012 Jan 18;32(3):995-1007. doi: 10.1523/JNEUROSCI.4755-11.2012.

Abstract

The three members of the Brn3 family of POU-domain transcription factors (Brn3a/Pou4f1, Brn3b/Pou4f2, and Brn3c/Pou4f3) are expressed in overlapping subsets of visual, auditory/vestibular, and somatosensory neurons. Using unmarked Brn3-null alleles and Brn3 conditional alleles in which gene loss is coupled to expression of an alkaline phosphatase reporter, together with sparse Cre-mediated recombination, we describe the following: (1) the overlapping patterns of Brn3 gene expression in somatosensory neurons; (2) the manner in which these patterns correlate with molecular markers, peripheral afferent arbor morphologies, and dorsal horn projections; and (3) the consequences for these neurons of deleting individual Brn3 genes in the mouse. We observe broad expression of Brn3a among DRG neurons, but subtype-restricted expression of Brn3b and Brn3c. We also observe a nearly complete loss of hair follicle-associated sensory endings among Brn3a(-/-) neurons. Together with earlier analyses of Brn3 gene expression patterns in the retina and inner ear, these experiments suggest a deep functional similarity among primary somatosensory neurons, spiral and vestibular ganglion neurons, and retinal ganglion cells. This work also demonstrates the utility of sparse genetically directed labeling for visualizing individual somatosensory afferent arbors and for defining cell-autonomous mutant phenotypes.

Publication types

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

MeSH terms

  • Animals
  • Axons / metabolism
  • Calcitonin Gene-Related Peptide / metabolism
  • Central Nervous System / cytology*
  • Eye Proteins / genetics
  • Female
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / physiology*
  • Glycoproteins / metabolism
  • Homeodomain Proteins / genetics
  • Male
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins / metabolism
  • Neurofilament Proteins / genetics
  • Neurofilament Proteins / metabolism
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors / genetics
  • Parvalbumins / metabolism
  • Protein Kinase C
  • Proteins / genetics
  • RNA, Untranslated
  • Repressor Proteins / genetics
  • SOXB1 Transcription Factors / genetics
  • Sensory Receptor Cells / classification
  • Sensory Receptor Cells / cytology*
  • Sensory Receptor Cells / metabolism*
  • Skin / innervation
  • Transcription Factor Brn-3 / genetics
  • Transcription Factor Brn-3 / metabolism*

Substances

  • Eye Proteins
  • Glycoproteins
  • Gt(ROSA)26Sor non-coding RNA, mouse
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Neurofilament Proteins
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Parvalbumins
  • Pax6 protein, mouse
  • Proteins
  • RNA, Untranslated
  • Repressor Proteins
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse
  • Transcription Factor Brn-3
  • isolectin B4-binding glycoprotein, mouse
  • neurofilament protein L
  • neurofilament protein H
  • protein kinase C gamma
  • Protein Kinase C
  • Calcitonin Gene-Related Peptide