TY - JOUR
T1 - Regulation of neurofibromin expression in rat sciatic nerve and cultured Schwann cells
AU - Wrabetz, Lawrence
AU - Feltri, Maria Laura
AU - Kim, Haesun
AU - Daston, Maryellen
AU - Kamholz, John
AU - Scherer, Steven S.
AU - Ratner, Nancy
PY - 1995/9
Y1 - 1995/9
N2 - Loss of function mutations at the NF1 locus may act intrinsically in Schwann cells to cause the formation of benign Schwann cell tumors (neurofibromas) in patients with type 1 neurofibromatosis. To identify contexts in Schwann cells in which such mutations may play an important role, we measured the levels of NF1 mRNA and neurofibromin in rat sciatic nerve during development, after axotomy, and in cultured rat Schwann cells. NF1 mRNA was present in developing sciatic nerve throughout the period of active Schwann cell proliferation and myelination. After nerve transection, no alteration in NF1 message level was detected, but neurofibromin levels increased, as assessed by immunohistochemistry and Western blotting, suggesting that, in vivo, neurofibromin expression in Schwann cells is post‐transcriptionally induced during Wallerian degeneration. Cultured rat Schwann cells constitutively expressed NF1 mRNA and neurofibromin. Schwann cell proliferation induced by exposure to serum and forskolin was not associated with changes in NF1 mRNA or neurofibromin expression, whereas Schwann cell proliferation induced by extracts of embryonic brain membranes was associated with increased NF1 message and neurofibromin expression. Thus, Schwann cells, both in vivo and in vitro, express NF1 mRNA constitutively; the expression of NF1 mRNA and neurofibromin is modulated by only some mitogenic stimuli in Schwann cells. © 1995 Wiley‐Liss, Inc.
AB - Loss of function mutations at the NF1 locus may act intrinsically in Schwann cells to cause the formation of benign Schwann cell tumors (neurofibromas) in patients with type 1 neurofibromatosis. To identify contexts in Schwann cells in which such mutations may play an important role, we measured the levels of NF1 mRNA and neurofibromin in rat sciatic nerve during development, after axotomy, and in cultured rat Schwann cells. NF1 mRNA was present in developing sciatic nerve throughout the period of active Schwann cell proliferation and myelination. After nerve transection, no alteration in NF1 message level was detected, but neurofibromin levels increased, as assessed by immunohistochemistry and Western blotting, suggesting that, in vivo, neurofibromin expression in Schwann cells is post‐transcriptionally induced during Wallerian degeneration. Cultured rat Schwann cells constitutively expressed NF1 mRNA and neurofibromin. Schwann cell proliferation induced by exposure to serum and forskolin was not associated with changes in NF1 mRNA or neurofibromin expression, whereas Schwann cell proliferation induced by extracts of embryonic brain membranes was associated with increased NF1 message and neurofibromin expression. Thus, Schwann cells, both in vivo and in vitro, express NF1 mRNA constitutively; the expression of NF1 mRNA and neurofibromin is modulated by only some mitogenic stimuli in Schwann cells. © 1995 Wiley‐Liss, Inc.
KW - GTPase‐activating protein
KW - NF1
KW - Neurofibromatosis
KW - Proliferation
KW - Wallerian degeneration
KW - ras
UR - http://www.scopus.com/inward/record.url?scp=0029360604&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029360604&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/glia.440150104
DO - https://doi.org/10.1002/glia.440150104
M3 - Article
C2 - 8847098
SN - 0894-1491
VL - 15
SP - 22
EP - 32
JO - Glia
JF - Glia
IS - 1
ER -