3 NEURAL TUBES IN MOUSE EMBRYOS WITH MUTATIONS IN THE T-BOX GENE TBX6

Somites, segmented mesodermal units of the vertebrate embryo, are the precursors of adult skeletal muscle, bone and cartilage(1). During emb ryogenesis, somite progenitor cells ingress through the primitive stre ak, move laterally to a paraxial position (alongside the body axis) an d segment into epithelial somites(2). Little is known about how this p araxial mesoderm tissue is specified(1,2). We have previously describe d a mouse T-box gene, Tbx6 (ref. 3), which codes for a putative DNA-bi nding protein(4,5). The embryonic pattern of expression of Tbx6 in som ite precursor cells suggests that this gene may be involved in the spe cification of paraxial mesoderm(3). We now report the creation of a mu tation in Tbx6 that profoundly affects the differentiation of paraxial mesoderm. Irregular somites form in the neck region of mutant embryos , whereas more posterior paraxial tissue does not form somites but ins tead differentiates along a neural pathway, forming neural-tube-like s tructures that flank the axial neural tube. These paraxial tubes show dorsal/ventral patterning that is characteristic of the neural tube, a nd have differentiated motor neurons, These results indicate that Tbx6 is needed for cells to choose between a mesodermal and a neuronal dif ferentiation pathway during gastrulation; Tbx6 is essential for the sp ecification of posterior paraxial mesoderm, and in its absence cells d estined to form posterior somites differentiate along a neuronal pathw ay.