Fig. 4.

MN diversification at limb levels. Exogenous RA from the paraxial mesoderm induces the generation of LMC neurons with LMCm identity. These cells rapidly initiate Raldh2 expression and RA synthesis, which promotes the generation of a later LMC population with LMCl identity. Hox proteins, possibly generic Hox5-8 paralogs, are necessary for high Foxp1 levels in the brachial LMC. Cross-repressive interactions between Isl1 and Lhx1, respectively, expressed by LMCm and LMCl neurons, stabilize this segregation and determine settling position and axonal projection of MNs in each division. Upon the influence of intrinsic factors, including Hox proteins and their cofactors, and of target-derived signals, subdivision of LMC neurons proceeds further and results in the formation of motor pools that individually innervate single target muscles. RALDH2 retinaldehyde dehydrogenase 2, RA retinoic acid