Somitogenesis and development of primary motor neurons: The role of the homeobox uncx4.1

The gene uncx4.1 is a paired-type homeobox transcription factor, expressed during zebrafish embryonic development in branchial arches, somites, CNS and pronephric ducts. In particular, the expression at the somite level is detectable from 5ss stage and becomes progressively posteriorly and ventrally restricted to the presumptive myoblast cells in later stages. Interestingly, the progressive restriction of uncx4.1 activity anticipates and accompanies the appearance of the first outgrowing primary motor axons. Indeed, after uncx4.1 expression is not detected anymore in medial somitic cells, a ventrally projecting CaP motor axons emerge from the ventro-lateral spinal cord. In relation with muscle differentiation, double hybridizations showed that uncx4.1 expression precedes myoD activation in muscle precursor cells. Moreover, co-localization of uncx4.1 mRNA and Myosin protein (fibroblast marker) reveals a complementary distribution of the two molecules, suggesting that uncx4.1 activity steps back from maturing muscle cells. uncx4.1 seems to be negatively regulated by shh pathway, indeed shh overexpression abolishes uncx4.1 transcription. Analyses of the shh pathway zebrafish mutants (floating head (flh), cyclops (nodal), sonic you (shh) and you-too (gli2)) showed that the expression of the uncx4.1 gene extends abnormally from dorsal to ventral within somitic compartments, confirming the negative regulation. Currently, uncx4.1 functional characterization is performed by a morpholino mediated strategy. Spatio-temporal dynamics of uncx4.1 expression, along with functional experimental evidences, suggest a double role for the uncx4.1 gene, in guiding outgrowth of motor axons, and regulating cell cycle in muscle progenitors at the margin of each somite.