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

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.