Establishment of the left-right axis of the vertebrate embryo requires the coordinated activities of a large number of genes. Many mutations in human and mouse affect left right specification and result in severe developmental defects. Nodal, a member of the TGFbeta family expressed exclusively in the left lateral plate mesoderm, is a crucial left determinant. However, little is known about regulation of nodal expression in the mouse embryo. Most recently, antagonism of BMP signaling has been shown in chick as one molecular mechanism for inducing nodal on the left side. The relevance of this pathway in mouse will be studied using a transgenic approach in combination with in vitro embryo culture. Targeted mutation of Pitx2, the only known target of nodal signaling, causes only limited defect in L-R determination, indicating that nodal signals through additional target genes. Moreover, the genetic pathway on the right side is even more poorly understood. To further understand the molecular mechanism controlling L-R asymmetry, I propose to screen for genes differentially expressed on the left and right side using suppression subtractive hybridization.
