Requirement for mast cell growth factor for primordial germ cell survival in culture.
Mast-cell growth factor (MGF) is encoded by the murine steel (Sl) 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 Sl 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 PGCs while MGF is expressed in the surrounding mesenchyme, 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.
Dolci
S
S
Mammalian Genetics Laboratory, NCl-Frederick Cancer Research and Development Center, Maryland 21702-1201.
Williams
D E
DE
Ernst
M K
MK
Resnick
J L
JL
Brannan
C I
CI
Lock
L F
LF
Lyman
S D
SD
Boswell
H S
HS
Donovan
P J
PJ
D000818:Animals; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology*; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000502:physiology; D015870:Gene Expression; D005854:Germ Cells / Q000166:cytology*; D016298:Hematopoietic Cell Growth Factors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor; D014162:Transfection
D016298:Hematopoietic Cell Growth Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit