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Requirement for mast cell growth factor for primordial germ cell survival in culture

Naturevolume 352pages809811 (1991) | Download Citation

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Abstract

MAST-CELL growth factor (MGF) is encoded by the murine steel (SI) locus and is a ligand for the tyrosine kinase receptor protein encoded by the proto-oncogene c-kit at the murine dominant white spotting ( W) locus. Mutations at both these loci affect mast cells, primordial germ cells (PGCs), haemopoietic stem cells and melanocytes. In many SI and W mutants, the rapid proliferation of PGC that normally occurs between day 7 and 13.5 of embryonic development fails to occur. As c-kit is expressed in PGCs1,2 while MGF is expressed in the surrounding mesenchyme2,3, MGF might promote the proliferation of PGCs. Here we report that MGF is essential for PGC survival in culture, but does not stimulate PGC proliferation. Moreover, whereas both the transmembrane and soluble proteolytic cleavage forms of MGF stimulate mast-cell proliferation, soluble MGF has a relatively limited ability to support survival of PGCs in culture, thus explaining the sterility in mice carrying the steel-dickie (Sld) mutation, which encodes only a soluble form of MGF, and providing a functional role for a transmembrane growth factor.

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Affiliations

  1. Mammalian Genetics Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland, 21702-1201, USA

    • Susanna Dolci
    • , Mary K. Ernst
    • , Camilynn I. Brannan
    • , Leslie F. Lock
    •  & Peter J. Donovan
  2. Molecular Mechanisms of Carcinogenesis Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland, 21702-1201, USA

    • James L. Resnick
  3. Department of Experimental Hematology, Immunex Corporation, 51 University Street, Seattle, Washington, 98101, USA

    • Douglas E. Williams
  4. Department of Molecular Biology, Immunex Corporation, 51 University Street, Seattle, Washington, 98101, USA

    • Stewart D. Lyman
  5. Indiana University School of Medicine, Indianapolis, Indiana, 46202, USA

    • H. Scott Boswell
  6. Dipartimento di Sanita Pubblica e Biologia Cellulare, II Università degli Studi di Roma, Tor Vergata, Rome, 00173, Italy

    • Susanna Dolci

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