Figure 9. Schematic model of the MET-BRAF-PAX3 feedback loop enabling migration of limb muscle precursor cells.
(A) Activation and subsequent internalization of MET leads to activation of BRAF and transport via endosomal trafficking to a perinuclear position. (B) After translocation of BRAF into the nucleus BRAF phosphorylates and activates PAX3, which promotes sustained expression of Met and other PAX3 target genes enabling limb muscle precursor cell migration. (C) Inactivation of Braf in PAX3-expressing cells disrupts the regulatory feedback loop leading to arrest of limb muscle precursor cell migration and defective limb muscle development. NT: neural tube; DM: dermomyotome; SC: sclerotome; NC: notochord.