Distinct Caenorhabditis elegans HLH-8/twist-containing dimers function in the mesoderm

Dev Dyn. 2012 Mar;241(3):481-92. doi: 10.1002/dvdy.23734. Epub 2012 Jan 31.

Abstract

Background: The Caenorhabditis elegans basic helix-loop-helix (bHLH) factor HLH-8, the single Twist ortholog in the nematode genome, plays important roles in mesoderm development, including M lineage patterning and differentiation of vulval and enteric muscles. HLH-8 cooperates with HLH-2, the bHLH E/Daughterless ortholog, to regulate downstream target genes, but it is not known whether HLH-2 is an obligate partner for all HLH-8 functions.

Results: Using hlh-2 loss-of-function alleles and RNAi, we discovered that HLH-2 is required in the vulval muscles but not in M patterning or enteric muscle development. Additionally, we found that expressing tethered HLH-8/HLH-8 dimers in hlh-8 null animals rescued M patterning and enteric but not vulval muscle development.

Conclusions: These results support a model whereby HLH-8/HLH-8 homodimers function in M lineage patterning and enteric muscles and HLH-8/HLH-2 heterodimers function in the M-derived vulval muscles. Interestingly, the different dimers function in the same M lineage cells and the switch in dimer function coincides with vulval muscle differentiation. The use of distinct Twist dimers is evolutionarily conserved, and C. elegans provides a paradigm for future dissection of differential promoter regulation by these dimers at a single cell resolution.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Body Patterning
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Female
  • Intestinal Mucosa / metabolism
  • Male
  • Mesoderm / cytology
  • Mesoderm / metabolism*
  • Muscle, Smooth / embryology*
  • Muscle, Smooth / metabolism*
  • Organ Specificity
  • Protein Multimerization
  • Twist-Related Protein 1 / genetics
  • Twist-Related Protein 1 / metabolism*
  • Vulva / embryology
  • Vulva / physiology

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Caenorhabditis elegans Proteins
  • HLH-2 protein, C elegans
  • HLH-8 protein, C elegans
  • Twist-Related Protein 1