Twist is an integrator of SHH, FGF, and BMP signaling

Development of vertebrate embryos is regulated by a number of different signaling pathways. These pathways are frequently not independent of each other but are connected by crosstalk between cells and tissues. Furthermore, different signaling pathways have been found to interact at the cellular level. Development of cranial and limb structures is an example, in which FGF, BMP, and SHH signaling interact. Mutations in the different signaling pathways may therefore result in complex but similar phenotypes. This indicates the existence of integrator molecules, which depend in their expression or activity on the combination of different signaling pathways. Here we show that expression of the bHLH transcription factor Twist in the paraxial mesoderm requires an induction from the notochord. This induction can only be substituted by a combination of FGF and SHH signaling, but not by individual application of FGF8 or SHH alone. Furthermore, the expression of Twist can be modified by BMP2 in a complex, age-dependent manner. We propose that Twist is one of the integrating parts of the three signaling pathways and mediates some of the common effects.