Growth regulation during mouse limb development
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Description
Mechanisms regulating the growth and pattern formation of the developing limb remain largely unknown. The approach which we have developed is based on using established cell lines as probes to monitor the embryonic environment. The attraction for using cell lines as probe for biological activity is twofold; (1) the tremendous number of murine cell line which have been developed of which very little is known regarding their biological activity during embryogenesis in vivo, (2) the relative ease with which cell line can be genetically manipulated through transfection and/or viral infection. In developing this approach we first developed a reliable means of labeling cells, and second we developed both in vivo and in vitro approaches designed at testing limb cells for their biological activity In our studies we have used 3T3 cells, an embryonic fibroblast cell line, to test for mitogenic and morphogenetic signals regulating limb development. We found that 3T3 cells appear sensitive to mitogenic signals which are being produced by limb cells both in vivo and in vitro. Interestingly, the growth of 3T3 cells directly correlates with the growth of limb cells, and that this correlation is maintained along the proximal-distal axis. 3T3 cells also appear to be responsive to signals which are involved in the recruitment of cells into a variety of limb mesodermal structures (i.e. connective tissues). The results from our studies indicate that continual cell-cell or cell-matrix interactions are occurring throughout limb development, thus limb development cannot be entirely explained by cell autonomy environment. Furthermore, it appears that the signals involved in the growth and morphological regulation of 3T3 cells are locally available, thus arguing against the presence of diffusible signals In this dissertation we have described an approach which utilizes 3T3 cells as probes for biological activity of the embryonic activity. We feel that combining both in vivo and in vitro approaches greatly enhances our chances of isolating developmentally important signals involved in the regulation of growth and patterning during limb development