The Caenorhabditis elegans MYOD homologue HLH-1 is essential for proper muscle function and complete morphogenesis

Abstract

A family of muscle-specific helix-loop-helix transcription factors (myoD, myogenin, myf-5 and MRF4) has been implicated in the control of vertebrate skeletal myogenesis. 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. We have isolated a null allele of hlh-1 following chemical mutagenesis. Animals homozygous for the null mutation produce contractile body-wall muscles, although muscle contractions are weak and coordination is defective. In addition to the evident muscle defects, mutant animals fail to complete embryonic elongation and die as larvae or young adults. Ultrastructural analysis of the mutant muscle reveals an apparently normal local lattice of thick and thin filaments, with more global defects in sarcomere organization and muscle cell placement. 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.

The complete cell atlas of an aging multicellular organism

“…We identified a total of 1,048 tissue-specific associations of the TF expression with its target genes’ activity across the atlas (Table S6). Many TF-cell type relationships are supported by previous publications, such as body-wall muscle specific HLH-1 activity (Figure 2C), seam cell-specific ELT-1 activity, intestine-specific ELT-7 activity, and IL2 neuron-specific DAF-19 activity (Figure S2) (Brabin et al, 2011; Chen et al, 1994; De Stasio et al, 2018; Sommermann et al, 2010).…”

A 4D single-cell protein atlas of transcription factors delineates spatiotemporal patterning during embryogenesis

“…2) (Maduro et al, 2015), MS (tbx-35 and ceh-51) (Broitman- Maduro et al, 2009), C (vab-7) (Ahringer, 1996) and multiple lineages (tbx-8 and tbx-9) (Andachi, 2004), along with those specifically expressed in the neuron (ceh-10 and lim-4) (Svendsen and McGhee, 1995;Zheng et al, 2005), pharynx (pha-4, pha-2, tbx-2, and ceh-22) (Kalb et al, 1998;Miyahara et al, 2004;Okkema and Fire, 1994;Raharjo et al, 2011), skin (elt-1, elt-3, lin-26, nhr-23, nhr-25) (Gilleard et al, 1999;Gissendanner and Sluder, 2000;Kostrouchova et al, 1998;Labouesse et al, 1996;Page et al, 1997), body muscle (hnd-1, hlh-1 and unc-120) (Chen et al, 1994;Fukushige et al, 2006;Mathies et al, 2003) and intestine (end-3, end-1, elt-7, elt-2, pqm-1, dve-1, and mdl-1) (Dowen et al, 2016;Maduro et al, 2015;Reece-Hoyes et al, 2007;Yuan et al, 1998).…”

Direct inhibition of G1 cdk kinase activity by MyoD promotes myoblast cell cycle withdrawal and terminal differentiation

“…The cdk4‐binding domain itself has been relatively well conserved in the MyoD proteins of mammals, but the amino acid sequence homology is reduced in the MyoD‐related proteins from the lower vertebrates and is only partially conserved in the invertebrate MyoD family members characterized to date (Table I). Preliminary experiments indicate that the MyoD homologs from Drosophila ( nautilus ) (Paterson et al ., 1991) and Caenorhabditis elegans ( hlh‐1 ) (Chen et al ., 1994) can specifically bind vertebrate cdk4 and can inhibit cell growth in the BrdU incorporation assay. The cdk4‐binding domains have not yet been characterized in either of these proteins but the conservation of the bHLH domain within the MyoD family suggests that binding does not involve this region since only MyoD bound cdk4.…”