The Notch signalling pathway regulates cell fate and differentiation decisions during development. Constitutive activation of Notch signalling represses differentiation and induces proliferation in many cell systems, and is associated with human neoplasias. Findings in cell culture and in invertebrates implicate Notch signalling in skeletal myogenesis, but there remains no supporting evidence in vivo in mammalian embryos. The hypothesis that Notch pathway regulators repress myogenesis will be directly tested by targeting mouse myf5, the earliest expressed myogenic determination gene, with a dominant active notch1 allele, NICD. Under the direction of myf5 regulatory elements, myf5NICD should be expressed in muscle precursor cells from early myogenesis to terminal muscle differentiation. Anatomical and molecular analysis of skeletal myogenesis and other myf5-dependent development processes will be performed on heterozygote and homozygote knock-in mouse embryos. These experiments offer insight into the role of Notch signalling throughout myogenesis in vivo.
