Nature 352, 807 - 809 (29 August 1991); doi:10.1038/352807a0

Effects of the steel gene product on mouse primordial germ cells in culture

I. Godin^*, R. Deed^†, J. Cooke^*, K. Zsebo^‡, M. Dexter^† & C. C. Wylie^*

^*Wellcome/CRC Institute and Department of Zoology, University of Cambridge, Tennis Court Road, Cambridge CB21QR, UK
^†Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital and Holt Radium Institute, Wilmslow Road, Withington, Manchester M20 9BX, UK
^‡AMGEN Inc., AMGEN Center, Thousand Oaks, California 91320, USA

MUTATIONS at the steel (si) and dominant white spotting (W) loci in the mouse affect primordial germ cells (PGC), melanoblasts and haemopoietic stem cells¹. The W gene encodes a cell-surface receptor of the tyrosine kinase family^2,3, the proto-oncogene c-kit. In situ analysis has shown c-kitmessenger RNA expression in PGC in the early genital ridges⁴. The SI gene encodes the ligand for this receptor, a peptide growth factor, called here stem cell factor (SCF) ^5–7. SCF mRNA is expressed in many regions of the early mouse embryo, including the areas of migration of these cell types⁸. It is important now to identify the role of the Sl-W interaction in the development of these migratory embryonic stem cell populations. Using an in vitro assay system⁹, we show that SCF increases both the overall numbers and colony sizes of migra-tory PGC isolated from wild-type mouse embryos, and cultured on irradiated feeder layers of STO cells (a mouse embryonic fibroblast line). In the absence of feeder cells, SCF causes a large increase in the initial survival and apparent motility of PGC in culture. But labelling with bromodeoxyuridine shows that SCF is not, by itself, a mitogen for PGC. SCF does not exert a chemotropic effect on PGC in in vitro assays. These results suggest that SCF in vivo is an essential requirement for PGC survival. This demon-strates the control of the early germ-line population by a specific trophic factor.

References

1.	Silvers, W. K. in The Coat Colours of Mice: a Model for Mammalian Gene Action and Interaction 243−267 (Springer, New York, 1979).
2.	Chabot, B., Stephenson, D. A., Chapman, V. M., Besmer, P. & Bernstein, A. Nature 335, 88−89 (1988). | Article | PubMed | ISI | ChemPort |
3.	Geissler, E., Ryan, M. & Houseman, D. Cell 55, 185−192 (1988). | Article | PubMed | ISI | ChemPort |
4.	Orr-Urtreger, A. et al. Development 109, 911−923 (1990). | PubMed | ChemPort |
5.	Zsebo, K. M. et al. Cell 63, 195−201 (1990). | Article | PubMed | ISI | ChemPort |
6.	Martin, F. H. et al. Cell 63, 203−211 (1990). | Article | PubMed | ISI | ChemPort |
7.	Zsebo, K. M. et al. Cell 63, 213−224 (1990). | Article | PubMed | ISI | ChemPort |
8.	Matsui, Y., Zsebo, K. M. & Hogan, B. L. M. Nature 347, 667−669 (1990). | Article | PubMed | ISI | ChemPort |
9.	Godin, I., Wylie, C. C. & Heasman, J. Development 108, 357−363 (1990). | PubMed | ISI | ChemPort |
10.	Nocka, K., Buck, J., Levi, E. & Besmer, P. EMBO J. 9, 3287−99 (1990). | PubMed | ISI | ChemPort |
11.	Anderson, D. et al. Cell 63, 235−243 (1990). | Article | PubMed | ISI | ChemPort |
12.	Dolci, S. et al. Nature 352, 809−811 (1991). | Article | PubMed | ISI | ChemPort |
13.	Dexter, T. M., Heyworth, C. M., Spooncer, E. & Ponting, I. L. Phil. Trans. R. Soc. B 327, 85−98 (1990). | ChemPort |
14.	Donovan, P., Stott, D., Caims, L. A., Heasman, J. & Wylie, C. C. Cell 44, 831−838 (1986). | Article | PubMed | ChemPort |
15.	Maniatis, T., Fritsch, E. & Sambrook, J. Molecular Cloning (Cold Spring Harbor Laboratory, New York, 1987).