The events of pattern formation and tissue differentiation are now thought to be controlled in large part by the actions and interactions of peptide growth factors, their receptors, and transcription factors which may either be acted upon as a result of growth factor release or which may direct the synthesis of these factors and their receptors. Unfortunately, the pathways connecting these components remain unclear. Since many products currently under review by CBER belong to the category of growth regulatory molecules, it is important to understand their actions. We have therefore begun attempts to identify targets for important regulatory genes containing homeobox domains. At present, we have expressed one of these proteins for preparation of antisera and are in the process of doing the same for several other genes. These will be used for immunoaffinity purification of the DNA to which the regulatory proteins are bound; cloning and sequencing of this DNA will allow identification of the gene. We have also identified potential homeobox genes in zebrafish embryos, which possess several useful characteristics that may complement the work in amphibians. In addition, candidates for members of the TGF-beta receptor family have been identified with PCR technology. In future studies, we hope to exploit DNA-protein interactions to identify trans acting factors which regulate these and other molecules involved in signal transduction.
