Erschienen:
Proceedings of the National Academy of Sciences, 2007
Erschienen in:
Proceedings of the National Academy of Sciences, 104 (2007) 2, Seite 537-542
Sprache:
Englisch
DOI:
10.1073/pnas.0608281104
ISSN:
0027-8424;
1091-6490
Entstehung:
Anmerkungen:
Beschreibung:
<jats:p>
In vertebrates, skeletal myogenesis is initiated by the generation of myoblasts followed by their differentiation to myocytes and the formation of myofibers. The determination of myoblasts and their differentiation are controlled by muscle regulatory factors that are activated at specific stages during myogenesis. During late embryonic and fetal stages a distinct population of resident proliferating progenitor cells is the major source of myogenic cells. How the differentiation of myoblasts and progenitor cells is regulated is not clear. We show that in mouse embryos the Notch ligand Delta1 (
<jats:italic>Dll1</jats:italic>
) controls both differentiation of early myoblasts and maintenance of myogenic progenitor cells. Early dermomyotome-derived myoblasts are determined normally in
<jats:italic>Dll1</jats:italic>
mutant embryos, but their differentiation is accelerated, leading to a transient excess of myotomal muscle fibers. Similarly, migratory hypaxial myogenic cells colonize the limb buds and activate muscle regulatory factor expression normally, but muscle differentiation progresses more rapidly. Resident progenitor cells defined by Pax3/Pax7 expression are formed initially, but they are progressively lost and virtually absent at embryonic day 14.5. Muscle growth declines beginning around embryonic day 12, leading to subsequent severe muscle hypotrophy in hypomorphic
<jats:italic>Dll1</jats:italic>
fetuses. We suggest that premature and excessive differentiation leads to depletion of progenitor cells and cessation of muscle growth, and we conclude that
<jats:italic>Dll1</jats:italic>
provides essential signals that are required to prevent uncontrolled differentiation early and ensure sustained muscle differentiation during development.
</jats:p>