REGULATED EXPRESSION OF NEUROFIBROMIN IN MIGRATING NEURAL CREST CELLSOF AVIAN EMBRYOS

Neurofibromatosis type 1 (NF1) is a common human genetic disease invol ving various neural crest (NC)-derived cell types, in particular, Schw ann cells and melanocytes. The gene responsible for NF1 encodes the pr otein neurofibromin, which contains a domain with amino acid sequence homology to the ras-guanosine triphosphatase activating protein, sugge sting that neurofibromin may play a role in intracellular signaling pa thways regulating cellular proliferation or differentiation, or both. To determine whether neurofibromin plays a role in NC cell development , we used antibodies raised against human neurofibromin fusion protein s in western blot and immunocytochemical studies of early avian embryo s. These antibodies specifically recognized the 235 kD chicken neurofi bromin protein, which was expressed in migrating trunk and cranial NC cells of early embryos (E1.5 to E2), as well as in endothelial and smo oth muscle cells of blood vessels and in a subpopulation of non-NC-der ived cells in the dermamyotome. At slightly later stages (E3 to E5), n eurofibromin immunostaining was observed in various NC derivatives, in cluding dorsal root ganglia and peripheral nerves, as well as non-NC-d erived cell types, including heart, skeletal muscle, and kidney. At st ill later stages (E7 to E9), neurofibromin immunoreactivity was found in almost all tissues in vivo. To determine whether the levels of neur ofibromin changed during melanocyte and Schwann cell development, tiss ue culture experiments were performed. Cultured NC cells were found to express neurofibromin at early time points in culture, but the levels of immunoreactivity decreased as the cells underwent pigmentation. Sc hwann cells, on the other hand, continued to express neurofibromin in culture. These data suggest, therefore, that neurofibromin may play a role in the development of both NC cells and a variety of non-NC-deriv ed tissues. (C) 1995 John Wiley and Sons, Inc.