CXCR4 and SDF1 are part of the core regulatory mechanism regulating migration of muscle precursor cells to the developing limb
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The ligand CXCR4 and its receptor SDF1 have been associated on several occacions with the formation of the limb musculature, specifically SDF1/CXCR4 signaling has been implicated to be associated with migration of the limb muscle precursor cells. In this thesis I will provide an overview of SDF1/CXCR4 signaling and how this pleiotropic signaling cascade could be involved in the regulation of the core mechanism regulation migration of limb muscle precursor cells. These interactions point to a top role of FGFs, SF/HGF and Shh in the limb bud mesenchyme to control both CXCR4 and SDF1 signaling, either directly (SDF1, CXCR4) or potentially through other factors such as NF-kB. Downstream of CXCR4 three potentially interesting mechanism can be distinguished. First JAK/STAT signaling which is also controlled by EphA4 which is also expressed in the migrating muscle precursors. Second a positive feedback loop of CXCR4 involving SHIP2, PI-3K and NF-kB. Third we can distinguish a potential mechanism by which CXCR4 regulates c-met by signaling through MAPK and Gab1.