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. Developmental Dynamics 241:481–492, 2012. © 2012 Wiley Periodicals, Inc.