Disease relevance of hlh-1

• We show here that overexpression of the Dyb-1 protein delays the onset of the myopathy observed in the C. elegans double mutant (dys-1; hlh-1 mutations) [1].

High impact information on hlh-1

• To assess the role of hlh-1 in C. elegans myogenesis, genetic deficiencies spanning the hlh-1 locus were isolated after gamma irradiation [2].
• Searches for homologs in the nematode Caenorhabditis elegans yielded only one gene, designated hlh-1, expressed in body-wall muscle cells and their precursors [2].
• Two-thirds of the Tc1-containing introns removed from hlh-1 and unc-54 lack either the 5'-GU or AG-3' dinucleotides typically found at the termini of eukaryotic introns [3].
• Earlier observations suggest that factors outside of the MyoD family might function redundantly with MyoD in striated muscle fate specification in these organisms [4].
• We find that the Caudal-related homeobox factor PAL-1 can activate hlh-1 in blastomeres that either lack POP-1/TCF or that have down-regulated POP-1/TCF in response to Wnt/MAP kinase signaling [5].

Biological context of hlh-1

• This result allowed us to look for genes that, when misexpressed, could suppress the dys-1; hlh-1 phenotype [6].
• We have isolated a null allele of hlh-1 following chemical mutagenesis [7].
• Mosaic studies using the point mutation and an extrachromosomal transgene indicate that the requirement for hlh-1 is fully zygotic, with no maternal hlh-1 requirement for either muscle development or viability [7].
• The predicted three-dimensional model of the homeodomain of CEH-37, which has a typical helix-loop-helix structure, was similar to that of the Myb domain of known telomere-binding proteins, which is also a helix-loop-helix protein, despite little amino acid sequence similarity [8].
• Furthermore, as a result of an additional polyploidy that occurred during the evolution of some amphibians and fish, MyoD, myogenin, myf5 and MRF4 may exist in lower vertebrates in two distinct copies that have evolved separately, acquiring specific roles and resulting in increased complexity of the myogenic regulatory network [9].

Anatomical context of hlh-1

• By ectopically expressing hlh-1 in early blastomeres of the C. elegans embryo, we show that CeMyoD is a bona fide MRF that can convert almost all cells to a muscle-like fate, regardless of their lineage of origin [5].
• These muscle cells all express the gene hlh-1, encoding HLH-1 (CeMyoD) which is the only MRF-related factor in the nematode [5].
• Searches for homologues of this family in Caenorhabditis elegans identified a single family member, hlh-1, which is expressed in striated muscles and their clonal precursors [7].
• MyoD and the specification of muscle and non-muscle fates during postembryonic development of the C. elegans mesoderm [10].

Associations of hlh-1 with chemical compounds

• Four members, MyoD, myogenin, myf5 and MRF4/herculin/myf6, have been identified in higher vertebrates and have been shown to exhibit distinct but overlapping functions [9].

Other interactions of hlh-1

• These blocked embryos remain viable for days and express a number of biochemical markers of early differentiation, for example, gut granules, the gut esterase ges-1, and two regulatory genes, mab-5 and hlh-1 [11].

Analytical, diagnostic and therapeutic context of hlh-1

• In the model animal Caenorhabditis elegans, mutations of the dys-1 dystrophin-like gene lead to a muscular degenerative phenotype when they are associated with a mild MyoD mutation [12].

References