The anterior/posterior polarity of somites is disrupted in paraxis-deficient mice

Establishing the anterior/posterior (A/P) boundary of individual somites is important for setting up the segmental body plan of all vertebrates. Reseg mentation of adjacent sclerotomes to form the vertebrae and selective migra tion of neural crest cells during the formation of the dorsal root ganglia and peripheral nerves occur in response to differential expression of genes in the anterior and posterior halves of the somite. Recent evidence indica tes that the A/P axis is established at the anterior end of the presomitic mesoderm prior to overt somitogenesis in response to both Mesp2 and Notch s ignaling. Here, we report that mice deficient for paraxis, a gene required for somite epithelialization, also display defects in the axial skeleton an d peripheral nerves that are consistent with a failure in A/P patterning. E xpression of Mesp2 and genes in the Notch pathway were not altered in the p resomitic mesoderm of paraxis(-/-) embryos. Furthermore, downstream targets of Notch activation in the presomitic mesoderm, including EphA4, were tran scribed normally, indicating that paraxis was not required for Notch signal ing. However, genes that were normally restricted to the posterior half of somites were present in a diffuse pattern in the paraxis(-/-) embryos, sugg esting a loss of A/P polarity. Collectively, these data indicate a role for paraxis in maintaining somite polarity that is independent of Notch signal ing. (C) 2001 Academic Press.