The precise temporal and spatial patterns of growth factor gene and receptor expression during embryogenesis need to be determine before their precise role during mammalian development can be elucidated. In this proposal, we will determine the embryonic and fetal cell types expressing three specific growth factor genes, whose products affect mesodermally-derived cell types in vitro, and the receptor for one of these genes. 1. We will continue to localize cells expressing the insulin-like growth factor-2 (IGF-2) gene during rat embryogenesis using in situ hybridization. We will complement these studies by producing IGF- 2 specific antisera to determine whether all IGF-2 mRNA containing cells actually produce and/or store this peptide. 2. We will characterize the expression of the IGF-2 receptor during development. We will use receptor specific antisera to localize receptor containing cells immunocytochemically and compare this distribution with that of IGF-2 expressing cells. We will further determine whether this receptor functions in endocytosis of exogenous ligands in the fetus and/or released form the surface of fetal cells in order to further establish its function during development. 3. We will determine the embryonic sites of expression for transforming growth factor-alpha and basic fibroblast growth factor, two peptides that stimulate angiogenesis and proliferation of mesodermal derivatives in vitro. The spatial and temporal patterns of expression will be compared with IGF-2, which is known to be expressed in mesodermal derivatives in vivo. Taken together, these studies will describe the in vivo sites of expression of these developmentally important genes and determine whether these growth factors are coordinately expressed in identical cell populations, whether expression is correlated with changes in proliferation and differentiation, whether effects of these factors are likely autocrine, paracrine, or endocrine, and will provide a basis for evaluating the results of in vivo perturbation of normal growth factor gene expression.
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