Studies in Dr. Little; laboratory strongly suggest that laminin plays a fundamental role in the mesenchymal cell migrations during cardiac development. Based on this work, he hypothesizes that laminin is one of the components to which mesenchymal cells adhere during their migration through cell-free regions of the early embryonic heart. The general goal of this proposal is to investigate this possibility using stage 6-12 chicken embryos. Specifically, Dr. Little proposes: 1) To purify chicken laminin for immunogen, then to isolate antibodies which recognize the various laminin chains (A, B1, B2). 2) to partially characterize chicken laminin. 3) to use recombinant DNA probes, derived from the mouse laminin gene, as a means of isolating hybridization probes to the chicken laminin gene. 4) To use the immunological and hybridization probes a means of determining the spatial and temporal distribution of laminin and its mRNA in early chicken hearts. 5) To investigate the cell biological effects of perturbing cell surface:laminin adhesion by use of the Tyr-Ile- Gly-Ser-Arg (YIGSR) laminin-derived peptide. and 6) To monitor cell surface interactions by immunolabeling specific cell adhesion molecules (N-CAM, A-CAM and the 67 kDa laminin receptor molecule) in untreated embryonic hearts, and hearts after injection with YIGSR. %%% The developing chicken heart is an excellent model system for studying the control of cell migration and adhesion. Cell migration and adhesion are driving influences in the embryonic development of animals. This study will provide valuable insights into these processes.
