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Journal of Neuroscience, Vol 16, 2012-2019, Copyright © 1996 by Society for Neuroscience
Identification of Gas6 as a growth factor for human Schwann cells
R Li, J Chen, G Hammonds, H Phillips, M Armanini, P Wood, R Bunge, PJ Godowski, MX Sliwkowski and JP Mather
Genentech, Inc., South San Francisco, California 94080, USA.
Schwann cells are one of the principal components of the peripheral nervous
system. They play a crucial role in nerve regeneration and can be used
clinically in the repair of injured nerves. We have established serum-free,
defined culture conditions that rapidly expand adult human Schwann cells
without fibroblast growth. We find that Gas6, a ligand for the Axl and
Rse/Tyro3 receptor protein tyrosine kinase family, stimulates human Schwann
cell growth, increasing both cell number and thymidine incorporation. Gas6
has synergistic effects with the other known human Schwann cell mitogens,
heregulin/glial growth factor and forskolin. Addition of Gas6 causes
phosphorylation of Axl and Rse/Tyro3 simultaneously and results in ERK-2
activation. A combination of Gas6 with heregulin and forskolin, on a
defined background, supports maximal Schwann cell proliferation, while
preserving the typical Schwann cell morphology and expression of the
Schwann cell markers S-100, glial fibrillary acidic protein, and
low-affinity nerve growth factor receptor. Gas6 mRNA is present in both
spinal motor neurons and large neurons of the dorsal root ganglia, and
neural injury has been reported to upregulate Rse/Axl in the schwann cell.
This is the first demonstration of a potentially important biological role
for the human Gas6/Rse-Axl system.
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