Repression of XMyoD expression and myogenesis by Xhairy-1 in Xenopus early embryo.
Activated Notch-Delta signalling was shown to inhibit myogenesis, but whether and how it regulates myogenic gene expression is not clear. We analyzed the implication of Xenopus hairy-1 (Xhairy-1), a member of the hairy and enhancer-of-split (E(spl)) family that may function as nuclear effector of Notch signalling pathway, in regulating XMyoD gene expression at the initial step of myogenesis. Xhairy-1 transcripts are expressed soon after mid-blastula transition and exhibits overlapping expression with Notch pathway genes such as Delta-1 in the posterior somitic mesoderm. We show that overexpression of Xhairy-1 blocks the expression of XMyoD in early gastrula ectodermal cells treated with the mesoderm-inducing factor activin, and in the mesoderm tissues of early embryos. It inhibits myogenesis and produces trunk defects at later stages. Xhairy-1 also inhibits the expression of the pan-mesodermal marker Xbra, but expression of other early mesoderm markers such as goosecoid and chordin is not affected. These effects require the basic helix-loop-helix (bHLH) domain, as well as a synergy between the central Orange domain and the C-terminus WRPW-Groucho-interacting domain. Furthermore, overexpression in ectodermal cells of Xhairy-1/VP16, in which Xhairy-1 repressor domain is replaced by the activator domain of the viral protein VP16, induces the expression of XMyoD in the absence of protein synthesis. Interestingly, Xhairy-1/VP16 does not induce the expression of Xbra and XMyf5 in the same condition. During neurulation, the expression of XMyoD induced by Xhairy-1/VP16 declines and the expression of muscle actin gene was never detected. These results suggest that Notch signalling through hairy-related genes may specifically regulate XMyoD expression at the initial step of myogenesis in vertebrates.
Umbhauer
M
M
Groupe de Biologie Expérimentale, Laboratoire de Biologie du Développement, CNRS UMR 7622, Université Pierre et Marie Curie, 9 quai Saint-Bernard, 75005, Paris, France.
Boucaut
J C
JC
Shi
D L
DL
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001665:Binding Sites; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins; D051956:Goosecoid Protein; D018257:Helix-Loop-Helix Motifs; D018398:Homeodomain Proteins / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins; D008648:Mesoderm; D024510:Muscle Development / Q000502:physiology*; D009124:Muscle Proteins / Q000235:genetics; D017570:MyoD Protein / Q000235:genetics*; D051787:Myogenic Regulatory Factor 5; D018994:Myosin Light Chains / Q000235:genetics; D011506:Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D020825:T-Box Domain Proteins / Q000235:genetics; D015534:Trans-Activators; D014157:Transcription Factors; D015533:Transcriptional Activation; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D006023:Glycoproteins; D051956:Goosecoid Protein; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D017570:MyoD Protein; D051787:Myogenic Regulatory Factor 5; D018994:Myosin Light Chains; D011506:Proteins; D012097:Repressor Proteins; D020825:T-Box Domain Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D029867:Xenopus Proteins; C405694:Hairy, HRT1 protein; C497419:Myf5 protein, Xenopus; C116765:TBXT protein, Xenopus; C054234:chordin