Regulation of Tbx6 expression by Notch signaling

Somites are the first overt sign of segmentation in the vertebrate embryo and form from bilateral strips of paraxial mesoderm. Paraxial mesoderm arises from the primitive streak; it then migrates laterally and comes to lie on both sides of the neural tube. In the mouse, the T-box transcription factor Tbx6 is required for both somite formation and patterning. Tbx6 expression corresponds both temporally and spatially to somite formation, with expression in the primitive streak and presomitic mesoderm. Its expression in the latter could simply be explained by maintenance following its initial activation in the primitive streak. Alternatively, its expression in the presomitic mesoderm may be contributed by separate regulatory elements possibly under the control of different signals. We have begun to investigate how Tbx6 expression is controlled during development using a transgenic approach to identify the cis-acting regulatory regions. We show that it is possible to separate an element required for presomitic mesoderm expression from that driving expression in the primitive streak. Further, we show that a binding site for the Notch transcription factor RBP-Jkappa is necessary for Tbx6 presomitic mesoderm enhancer activity, indicating that Notch signaling is upstream of Tbx6 in the pathway directing somite formation and patterning.