Antibodies to liver cell adhesion molecule perturb inductive interactions and alter feather pattern and structure

Abstract

Cell adhesion molecules (CAMs) may act as regulators of morphogenesis by constraining cell motion, forming borders, and controlling intercellular communications that lead to embryonic induction. This postulated causal role of CAMs in inductive events was tested here in an in vitro system of feather induction. In the developing chicken skin, an ectodermal sheet of epithelium interacts with mesodermal cell collectives to form more or less circular feather germs arranged in a hexagonal pattern. Cells of the epidermal epithelium are linked by liver CAM (L-CAM) and mesodermal cells in dermal condensations are linked by neural CAM (N-CAM); neither of these CAMs links cells in one tissue of this inductive couple to cells in the other. After perturbation of the L-CAM linkage in epidermis by antibodies to L-CAM, nonhexagonal striped patterns of dermal condensations were observed in culture. The stripes did not follow straight lines but meandered in lateral and oblique directions. Histological examination of the perturbed tissues showed extensive changes in dermal cell density distributions. After 10 days of culture, the perturbed tissues developed a cobbled or plaque-like morphology resembling scales rather than the feather-like filamentous structures that formed in unperturbed skin cultures. The results indicate that perturbation of CAM binding in tissues linked by one CAM can alter fates and interactions of cells linked by another, presumably by altering the amount or effect of inductive signals crossing the border between the inducing cell collectives. A computer model based on the notion that the response of L-CAM-linked epidermal cells to signals from N-CAM-linked dermal cells depends cooperatively on the degree of L-CAM linkage was found to generate hexagonal patterns for the unperturbed case and stripes after perturbation of L-CAM bonds.