S19-01 Planarians, stem cells, and regeneration

ical role in regulating their entry into the myogenic programme. We had shown that in the Pax3/7 double mutant the myogenic determination genes, Myf5 and MyoD are not activated, leading to a major deficit in skeletal muscle. Pax3 directly activates Myf5, thus promoting a myogenic cell fate. However, it is essential to maintain a balance between differentiation and renewal of the progenitor cell population. We show that this can be achieved by Pax3 modulation of FGF signaling via Sprouty1 and Fgfr4, which is a direct Pax3 target. Other Pax3 targets will be discussed, including Dmrt2 and Foxc2, both expressed in the dermomyotome, the part of the somite from which skeletal muscle cells derive. Foxc2 is negatively regulated by Pax3 and in turn feeds back negatively on Pax3/7 expression. This negative feedback loop is implicated in cell fate decisions of the multipotent Pax3/7 positive stem cells of the dermomyotome. These cells can form derm, brown fat endothelial and smooth muscle cells of blood vessels as well as skeletal muscle. Taking the latter tissues as an example, we show genetically that up-regulation of Foxc2 promotes endothelial and smooth muscle cell fates whereas Pax3/7 promote myogenesis. This is also demonstrated by manipulation of these factors in somite explants. Signaling from adjacent tissues, such as the dorsal ectoderm, affects the equilibrium between Pax3/7:Foxc2 and the choice of cell fate of the multipotent cells expressing these genes in the dermomyotome.