ALTERATIONS IN GENE-EXPRESSION DURING MESODERM FORMATION AND AXIAL PATTERNING IN BRACHYURY (T) EMBRYOS

The mouse T (Brachyury) deletion ca uses defective mesoderm formation and notochord morphogenesis, and abnormalities in the caudal neural tu be and somites. To investigate the effect of the wild type T gene on c oncurrently expressed genes, we have compared expression of a panel of such genes in homozygous T mutants with that in wild type and heteroz ygous T/+ control embryos. Two classes of genes were used in this stud y: those implicated in primitive streak or mesoderm formation, and tho se which are differentially expressed in regions of the neural tube an d somites. Results of wholemount in situ analysis show that the mRNA l evels of Evx-1, Wnt-3a and Wnt-5a decrease in T/T embryos late in gast rulation, although earlier expression patterns are similar to control embryos. In contrast, BMP-4 and Msx-1 expression patterns remain simil ar throughout the period studied. Pax-3 and Pax-6, which are expressed in specific dorsoventral domains of the neural tube. both have ventra lly extended expression domains in caudal T/T neural tube. This is con sistent with a missing ventral signal provided by the notochord. Howev er, the expression of Msx-1 in the most dorsal domain of the neural tu be is unaltered in T/T embryos. Pax-1 and Pax-3, which are expressed i n the sclerotome and dermamyotome respectively, are expressed correctl y in anterior T/T somites, although the Pax-3 expression domain is wid ened ventromedially. This extension into ventromedial somite domains i s more pronounced caudally, supporting a function for the notochord in ventralizing somites.