Km. Stocker et al., REGULATED EXPRESSION OF NEUROFIBROMIN IN MIGRATING NEURAL CREST CELLSOF AVIAN EMBRYOS, Journal of neurobiology, 27(4), 1995, pp. 535-552
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.