Bmp signaling is at the heart of vertebrate left-right asymmetry

During embryo development, Bone Morphogenic Proteins (BMPs), members of the TGF-beta superfamily, are critically involved in the formation and differentiation of almost all organs and tissues, as well as the establishment of the basic body plan by specification of the dorsal-ventral axis during gastrulation. Loss of function analysis of BMPs and their intracellular signaling components in mouse has revealed the importance for BMP signaling during vertebrate development. Due to the early lethality of these mutants, the role of BMPs during later processes remains mainly unsolved. Using Xenopus and zebrafish it has been demonstrated that BMP signaling is required for dorsal-ventral (DV) patterning of the vertebrate embryo. Dorsal-ventral patterning mutants were isolated during a large mutagenesis screen in zebrafish and the mutations where later identified in BMP signaling components. Some of these mutants survive long enough to make it possible to study later roles for BMP signaling such as regulation of the development of the embryonic heart. Our preliminary results with these zebrafish mutants already indicate a requirement for some of the BMP signaling components during vertebrate heart development. In the proposed project these mutants will be used to address the question how BMPs regulate different aspects of heart development. Using knock-out technology developed here in the Hubrecht Laboratory additional mutants in several BMP signaling components will be screened for and these will be used in our analysis. This should lead to novel insights on the regulation of embryonic heart development by BMPs.