Glial growth factor restricts mammalian neural crest stem cells to a glial fate
Growth factors and cytokines are thought to influence the development of uncommitted progenitor cell populations, but the issue of how these factors act on individual cells remains controversial. Such factors may act simply as selective mitogens or survival factors for cells that undergo lineage restrictions stochastically. Alternatively, they may instruct or bias multipotent cells to choose one lineage at the expense of others. Here we show that glial growth factor (GGF), previously defined as a Schwann cell mitogen, strongly suppresses neuronal differentiation of rat neural crest stem cells while promoting or allowing glial differentiation. Quantitative clonal analysis suggests that the action of GGF is likely to be instructive rather than selective. Taken together with the expression pattern of GGF, these data suggest a lateral signaling model for the diversification of cell types within developing peripheral ganglia.
© 1994 Cell Press. Received February 25, 1994; Revised April 1, 1994. Correspondence should be addressed to D. J. A. For contributions to the production of purified rGGF2, we acknowledge D. Bedell-Hogan, M. Hendricks, and C. Kirk (Cambridge Neuroscience Incorporated). We thank P. Patterson, S. Fraser, P. Sternberg, K. Zinn, A. Groves (Caltech), D. Stemple(Massachusetts General Hospital), and members of the GGF group at Cambridge Neuroscience incorporated for their critical comments on the manuscript; L. Lo, T. Saito, J. Verdi, and C. Schoenherr for providing advice and reagents; and S. ht. Padilla for expert technical assistance. We also thank N. Mahanthappa (Cambridge Neuroscience Incorporated) for advice on anti-GGF antibody staining protocols. We are grateful to D. Stemple for teaching us the neural crest cell isolation technique and for helpful discussions. This work was supported in part by a grant from the Muscular Dystrophy Association. D. J. A. is an Associate Investigator of the Howard Hughes Medical Institute.