TY - JOUR
T1 - The protooncogene ski controls schwann cell proliferation and myelination
AU - Atanasoski, Suzana
AU - Notterpek, Lucia
AU - Lee, Hye Youn
AU - Castagner, François
AU - Young, Peter
AU - Ehrengruber, Markus U.
AU - Meijer, Dies
AU - Sommer, Lukas
AU - Stavnezer, Ed
AU - Colmenares, Clemencia
AU - Suter, Ueli
N1 - Funding Information:
We thank Drs. Bruno Amati, Bernard Massie, and Bert Vogelstein for plasmids; Drs. Alexander Gow, Michael Wegner, and Monica Oblinger for riboprobes; and Drs. Michael Tropak and Peter Brophy for antibodies. We are grateful to Drs. Mark Marchionni for recombinant GGF; Elizabeth Nabel for recombinant p21 adenovirus; and Ned Mantei for comments on the manuscript. Katja Wichmann, Joke Nowitzki, Lucilla Nobbio, and Dr. Regula Frei provided much appreciated technical assistance. This work was supported by grants from the National Muscular Dystrophy Association and the NIH-NINDS (to L.N.), the Kommission Inovative Forschung of the University of Münster (YO1021 to P.Y.), the Swiss National Science Foundation, the Swiss Muscle Disease Foundation, and the NCCR Neural Plasticity and Repair (to S.A., L.S., and U.S.), and by NIH grants CA43600 (to E.S.) and HD30728 (to C.C.).
PY - 2004/8/19
Y1 - 2004/8/19
N2 - Schwann cell proliferation and subsequent differentiation to nonmyelinating and myelinating cells are closely linked processes. Elucidating the molecular mechanisms that control these events is key to the understanding of nerve development, regeneration, nerve-sheath tumors, and neuropathies. We define the protooncogene Ski, an inhibitor of TGF-β signaling, as an essential component of the machinery that controls Schwann cell proliferation and myelination. Functional Ski overexpression inhibits TGF-β-mediated proliferation and prevents growth-arrested Schwann cells from reentering the cell cycle. Consistent with these findings, myelinating Schwann cells upregulate Ski during development and remyelination after injury. Myelination is blocked in myelin-competent cultures derived from Ski-deficient animals, and genes encoding myelin components are downregulated in Ski-deficient nerves. Conversely, overexpression of Ski in Schwann cells causes an upregulation of myelin-related genes. The myelination-regulating transcription factor Oct6 is involved in a complex modulatory relationship with Ski. We conclude that Ski is a crucial signal in Schwann cell development and myelination.
AB - Schwann cell proliferation and subsequent differentiation to nonmyelinating and myelinating cells are closely linked processes. Elucidating the molecular mechanisms that control these events is key to the understanding of nerve development, regeneration, nerve-sheath tumors, and neuropathies. We define the protooncogene Ski, an inhibitor of TGF-β signaling, as an essential component of the machinery that controls Schwann cell proliferation and myelination. Functional Ski overexpression inhibits TGF-β-mediated proliferation and prevents growth-arrested Schwann cells from reentering the cell cycle. Consistent with these findings, myelinating Schwann cells upregulate Ski during development and remyelination after injury. Myelination is blocked in myelin-competent cultures derived from Ski-deficient animals, and genes encoding myelin components are downregulated in Ski-deficient nerves. Conversely, overexpression of Ski in Schwann cells causes an upregulation of myelin-related genes. The myelination-regulating transcription factor Oct6 is involved in a complex modulatory relationship with Ski. We conclude that Ski is a crucial signal in Schwann cell development and myelination.
UR - http://www.scopus.com/inward/record.url?scp=4143131010&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2004.08.001
DO - 10.1016/j.neuron.2004.08.001
M3 - Article
C2 - 15312649
AN - SCOPUS:4143131010
SN - 0896-6273
VL - 43
SP - 499
EP - 511
JO - Neuron
JF - Neuron
IS - 4
ER -