title: Divergent and conserved roles of Dll1 signaling in development of craniofacial and trunk muscle.
abstract: Craniofacial and trunk skeletal muscles are evolutionarily distinct and derive from cranial and somitic mesoderm, respectively. Different regulatory hierarchies act upstream of myogenic regulatory factors in cranial and somitic mesoderm, but the same core regulatory network - MyoD, Myf5 and Mrf4 - executes the myogenic differentiation program. Notch signaling controls self-renewal of myogenic progenitors as well as satellite cell homing during formation of trunk muscle, but its role in craniofacial muscles has been little investigated. We show here that the pool of myogenic progenitor cells in craniofacial muscle of Dll1(LacZ/Ki) mutant mice is depleted in early fetal development, which is accompanied by a major deficit in muscle growth. At the expense of progenitor cells, supernumerary differentiating myoblasts appear transiently and these express MyoD. The progenitor pool in craniofacial muscle of Dll1(LacZ/Ki) mutants is largely rescued by an additional mutation of MyoD. We conclude from this that Notch exerts its decisive role in craniofacial myogenesis by repression of MyoD. This function is similar to the one previously observed in trunk myogenesis, and is thus conserved in cranial and trunk muscle. However, in cranial mesoderm-derived progenitors, Notch signaling is not required for Pax7 expression and impinges little on the homing of satellite cells. Thus, Dll1 functions in satellite cell homing and Pax7 expression diverge in cranial- and somite-derived muscle.
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Maciej T
authors.initials: MT
authors.lastname: Czajkowski
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Rassek
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Diana C
authors.initials: DC
authors.lastname: Lenhard
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bröhl
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany. Electronic address: cbirch@mdc-berlin.de.
authors.forename: Carmen
authors.initials: C
authors.lastname: Birchmeier
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D017931:DNA Primers / Q000235:genetics; D005152:Facial Muscles / Q000196:embryology*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009024:Morphogenesis / Q000502:physiology*; D018482:Muscle, Skeletal / Q000196:embryology*; D051763:PAX7 Transcription Factor / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D060726:Torso / Q000196:embryology*
chemical_list: D002135:Calcium-Binding Proteins; D017931:DNA Primers; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; D051880:Receptors, Notch
keywords: Craniofacial muscles; Dll1; Myogenic progenitor cells; Notch signaling; Pax7