MyoD stimulates delta-1 transcription and triggers notch signaling in the Xenopus gastrula.
The Notch signaling cascade is involved in many developmental decisions, a paradigm of which has been the selection between epidermal and neural cell fates in both invertebrates and vertebrates. Notch has also been implicated as a regulator of myogenesis, although its precise function there has remained controversial. Here we show that the muscle-determining factor MyoD is a direct, positive regulator of the Notch ligand Delta-1 in prospective myoblasts of the pre-involuted mesoderm in Xenopus gastrulae. Injection of a dominant MyoD repressor variant ablates mesodermal Delta-1 expression in vivo. Furthermore, MyoD-dependent Delta-1 induction is sufficient to activate transcription from promoters of E(spl)-related genes in a Notch-dependent manner. These results indicate that a hallmark of neural cell fate determination, i.e. the feedback loop between differentiation promoting basic helix-loop-helix proteins and the Notch regulatory circuitry, is conserved in myogenesis, supporting a direct involvement of Notch in muscle determination.
Wittenberger
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Friedrich Miescher Laboratory, MPG, Spemannstrasse 37-39, D-72076 Tübingen, Germany.
Steinbach
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OC
Authaler
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A
Kopan
R
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Rupp
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RA
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005246:Feedback; D005260:Female; D005775:Gastrula / Q000378:metabolism; D014644:Genetic Variation; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009132:Muscles / Q000196:embryology / Q000378:metabolism; D017570:MyoD Protein / Q000235:genetics* / Q000378:metabolism; D051880:Receptors, Notch; D015398:Signal Transduction; D014158:Transcription, Genetic; D014981:Xenopus / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism
D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D017570:MyoD Protein; D051880:Receptors, Notch; C064045:delta protein