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.
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.
Authors: C Murre; P S McCaw; H Vaessin; M Caudy; L Y Jan; Y N Jan; C V Cabrera; J N Buskin; S D Hauschka; A B Lassar Journal: Cell Date: 1989-08-11 Impact factor: 41.582
Authors: V el Ghouzzi; M Le Merrer; F Perrin-Schmitt; E Lajeunie; P Benit; D Renier; P Bourgeois; A L Bolcato-Bellemin; A Munnich; J Bonaventure Journal: Nat Genet Date: 1997-01 Impact factor: 38.330
Authors: A O Wilkie; S F Slaney; M Oldridge; M D Poole; G J Ashworth; A D Hockley; R D Hayward; D J David; L J Pulleyn; P Rutland Journal: Nat Genet Date: 1995-02 Impact factor: 38.330
Authors: Sharon Kim; Stephen R F Twigg; Victoria A Scanlon; Aditi Chandra; Tyler J Hansen; Arwa Alsubait; Aimee L Fenwick; Simon J McGowan; Helen Lord; Tracy Lester; Elizabeth Sweeney; Astrid Weber; Helen Cox; Andrew O M Wilkie; Andy Golden; Ann K Corsi Journal: Hum Mol Genet Date: 2017-06-01 Impact factor: 6.150