Prior to the specification of skeletal muscle lineage, anterior–posterior elongation of the body axis and accompanying segmentation of paraxial mesoderm are partly regulated by opposing gradients of RA and fibroblast growth factor (Fig. Retinoic acid (RA), a derivate of vitamin A, is a morphogen that plays many important roles in vertebrate embryonic development.
Several signaling molecules involved in the progression of myogenic specification and commitment are differentially regulated by bexarotene and RA, suggesting that early targets of rexinoid allow the coordinated regulation of molecular events which leads to efficient myogenic differentiation in ES cells.ĭuring vertebrate embryogenesis, the progression of skeletal myogenesis is regulated by coordinated signaling pathways that induce the sequential expression of a range of key developmental transcription factors. Interestingly, bexarotene induces the early expression of a myogenic progenitor marker, Meox1, while the expression of many RA targets is also enhanced by bexarotene. Thus profiling the transcriptomes of ES cells differentiated with bexarotene or RA permits the identification of different genetic targets and signaling pathways that may contribute to the difference of bexarotene and RA in efficiency of myogenesis. Nevertheless, bexarotene, a clinically approved rexinoid, enhances the specification and differentiation of ES cells into skeletal myocytes more effectively than RA. During vertebrate development, retinoic acid (RA) plays an important role in body axis elongation and mesoderm segmentation in that graded exposure to RA provides cells with positional identity and directs commitment to specific tissue lineages. Regulation of lineage specification and differentiation in embryonic stem (ES) cells can be achieved through the activation of endogenous signaling, an avenue for potential application in regenerative medicine.