Zebrafish tbx-c functions during formation of midline structures

Several genes containing the conserved T-box region in invertebrates and ve rtebrates have been reported recently. Here, we describe three novel member s of the T-box gene family in zebrafish, One of these genes, tbx-c, is stud ied in detail. It is expressed in the axial mesoderm, notably, in the notoc hordal precursor cells immediately before formation of the notochord and in the chordoneural hinge of the tail bud, after the notochord is formed. In addition, its expression is detected in the ventral forebrain, sensory neur ons, fin buds and excretory system. The expression pattern of tbx-e differs from that of the other two related genes, tbx-a and tbx-b. The developmental role of tbx-c has been analysed by overexpression of the full-length tbx-e mRNA and a truncated form of tbx-c mRNA, which encodes th e dominant-negative Tbx-c, Overexpression of tbx-e causes expansion of the midline mesoderm and formation of ectopic midline structures at the expense of lateral mesodermal cells. In dominant-negative experiments, the midline mesoderm is reduced with the expansion of lateral mesoderm to the midline, These results suggest that tbx-e plays a role in formation of the midline mesoderm, particularly, the notochord, Moreover, modulation of tbx-e activi ty alters the development of primary motor neurons. Results of in vitro analysis in zebrafish animal caps suggest that tbx-e ac ts downstream of early mesodermal inducers (activin and ntl) and reveal an autoregulatory feedback loop between ntl and tbx-c, These data and analysis of midline (ntl(-/-) and flh(-/-)) and lateral mesoderm (spt(-/-)) mutants suggest that tbx-e may function during formation of the notochord.