Autocrine and paracrine mechanisms regulating primordial germ cell proliferation.
Although several mitogens and survival factors have been previously shown to act on primordial germ cells (PGCs) in culture, it is not clear whether they are responsible for controlling proliferation of PGCs in the embryo. We show here that during their migratory phase, PGCs do not express FGF-4, FGF-8, or FGF-17, but these FGFs are expressed by neighboring cells. Thus, any FGF action on migrating PGCs would appear to be through a paracrine mechanism. We found that after entering into the gonads, PGCs start to express FGF-4 and FGF-8. On this basis, we hypothesize that FGF signaling is involved in both a paracrine manner in initiating PGC proliferation during their migration and an autocrine manner in sustaining PGC proliferation after their arrival in the gonads. We then studied the role of soluble stem cell factor (SCF), which acts as a survival factor or a mitogen in culture, to determine whether it interacts with FGFs. We found that SCF has a complex effect on PGC proliferation. On one hand, soluble SCF promoted PGC proliferation synergistically with FGF in the absence of membrane-bound SCF. Conversely, soluble SCF inhibited FGF-stimulated proliferation of PGCs in the presence of membrane-bound SCF. We account for these findings in a model involving regulation of PGC proliferation, in which SCF modulates the response to FGFs.
Kawase
Eihachiro
E
Reproductive Genetics Unit, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, California, USA. eik@stowers-institute.org
Hashimoto
Koichiro
K
Pedersen
Roger A
RA
D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051519:Fibroblast Growth Factor 4; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D005854:Germ Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006066:Gonads / Q000166:cytology / Q000378:metabolism; D017403:In Situ Hybridization; D051379:Mice; D019899:Paracrine Communication / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D019089:Stem Cell Factor / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
C484726:Fgf17 protein, mouse; C496446:Fgf4 protein, mouse; C496457:Fgf8 protein, mouse; D051519:Fibroblast Growth Factor 4; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D019089:Stem Cell Factor; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors