THE ROLE(S) OF FRZB CHICK SOMITE PATTERNING

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DESCRIPTION (adapted from investigator's abstract): The development of a vertebrate organism from a single fertilized egg is a complex series of events involving both cell proliferation and specialization. Many of these events have been shown to be mediated by intercellular signals. To date, four families of secreted proteins that provide essential intercellular cues during development have been identified. These include the fibroblast growth factor (FGF) family, the hedgehog (Hh) family, the transforming growth factors (TGF-B) family, and the Wnt family. These protein families are involved in a variety of developmental processes and their mode of action has been highly conserved throughout evolution. The overall goal of this project is to understand the role(s) of these signals in directing chick somite cells to develop into either muscle, bone, or skin. Although these somite cells are initially pluripotential, cells located dorsally are instructed to become skeletal muscle whereas cells that are located ventrally are instructed to become axial skeleton (for review, see Christ and Ordahl, 1995). Wnt proteins are secreted signaling factors that have been shown to have opposing roles in inducing myogenesis and in repressing chondrogenesis (Munsterberg et al, 1995; Rudnicki and Brown, 1997; Capdevila et al, 1998). Recently, an antagonist of Wnt activity, called frzb, has been identified in a number of species (for review, see Moon et al, 1997). In the mouse,fab-1 is expressed in segmental plate and newly formed somites (Leyns et al, 1997), suggesting the exciting possibility that it may function as a negative regulator of Wnt activity in developing somites. The experiments described in this proposal are designed to answer some important questions pertaining to somite patterning. First, is there a chick homologue of frzb that is also expressed in segmental plate and/or somites? if so, does frzb act to inhibit myogenesis and/or promote chondrogenesis in developing somites? As we acquire a better understanding of the molecular cues required for skeletal muscle and bone specification, we will be paving the way for the development of techniques by which diseased or injured muscle tissue and/or bone can be regenerated. In addition, by establishing these types of interactions between signaling molecules, we are not only enhancing our knowledge of how muscle tissue is generated during normal development; we are also identifying regulatory motifs that may play a role in a variety of other developmental processes as well as cancer.