Postmitotic diversification of olfactory neuron types is mediated by differential activities of the HMG-box transcription factor SOX-2

EMBO J. 2015 Oct 14;34(20):2574-89. doi: 10.15252/embj.201592188. Epub 2015 Sep 4.

Abstract

Diversification of neuron classes is essential for functions of the olfactory system, but the underlying mechanisms that generate individual olfactory neuron types are only beginning to be understood. Here we describe a role of the highly conserved HMG-box transcription factor SOX-2 in postmitotic specification and alternative differentiation of the Caenorhabditis elegans AWC and AWB olfactory neurons. We show that SOX-2 partners with different transcription factors to diversify postmitotic olfactory cell types. SOX-2 functions cooperatively with the OTX/OTD transcription factor CEH-36 to specify an AWC "ground state," and functions with the LIM homeodomain factor LIM-4 to suppress this ground state and drive an AWB identity instead. Our findings provide novel insights into combinatorial codes that drive terminal differentiation programs in the nervous system and reveal a biological function of the deeply conserved Sox2 protein that goes beyond its well-known role in stem cell biology.

Keywords: C. elegans; homeodomain; neuron differentiation; sox‐2.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • COS Cells
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Differentiation / physiology*
  • Chlorocebus aethiops
  • Chromosome Mapping
  • Electrophoretic Mobility Shift Assay
  • Genome / genetics
  • Homeodomain Proteins / metabolism
  • LIM-Homeodomain Proteins / metabolism
  • Luciferases
  • Molecular Sequence Data
  • Olfactory Receptor Neurons / cytology
  • Olfactory Receptor Neurons / physiology*
  • Plasmids / genetics
  • SOXB1 Transcription Factors / metabolism*
  • Sequence Analysis, DNA
  • Transcription Factors / metabolism
  • Transfection

Substances

  • Caenorhabditis elegans Proteins
  • Homeodomain Proteins
  • LIM-Homeodomain Proteins
  • Lim-4 protein, C elegans
  • SOXB1 Transcription Factors
  • Transcription Factors
  • ceh-36 protein, C elegans
  • Luciferases