Role of Fibroblast Growth Factors and Their Receptors in Mouse Primordial Germ Cell Growth1

Abstract

Primordial germ cells (PGCs) are the embryonic progenitors of mature germ cells. During their proliferative stage, murine PGCs may be transiently cultured on mitotically inactive feeder layers. This culture system has permitted identification of several growth factors active toward PGCs. We and others have previously identified basic fibroblast growth factor (bFGF) as a powerful mitogen in this system. Here we characterize some of the functions of bFGF in PGC culture. Our data demonstrate that fibroblast growth factor (FGF) receptors I and II are present in the developing gonad and are consistent with expression of these receptors by PGCs. Moreover, PGCs can bind radiolabeled bFGF in vitro, demonstrating that the factor can act directly on these cells. While mitotic PGCs of either sex are shown to bind radiolabeled bFGF, oogonia that are undergoing meiotic arrest exhibit reduced bFGF binding, indicating potential developmental regulation of an FGF receptor.

Conditional loss of PTEN leads to testicular teratoma and enhances embryonic germ cell production

“…SCF, LIF and bFGF, are expressed in gonadal PGCs (Cheng et al, 1994;Pesce et al, 1997;Resnick et al, 1998). As Akt was hyper-activated in Pten mutant PGCs, it is likely that the loss of PTEN enhanced the PI3K signaling pathway, which then resulted in the deregulated differentiation of PGCs.…”

The roles of FGF signaling in germ cell migration in the mouse

“…FGF2 and FGF7, the high-affinity ligands for FGFR1-IIIc and FGFR2-IIIb, respectively, are each thought not to activate the other receptor. Effective doses for FGF2 and FGF7 are described as 100-250 ng/ml and <1000 ng/ml, respectively, in the manufacture's protocol, other published FGF studies have used a wide range of concentrations for these ligands, from 1-1000 ng/ml (Resnick et al, 1998;Weksler et al, 1999;Bridges et al, 2003;Kawase et al, 2004). Because FGF ligand-receptor interactions are influenced by many factors other than ligand concentration, such as heparin and cell-surface proteoglycans, it is impossible to determine what ligand concentrations in vitro will mimic physiological conditions.…”

“…FGF2 has been reported to act as a mitogen for PGCs in vitro, and, together with steel factor and LIF, causes cultured germ cells to change into pluripotential permanent cell lines (Matsui et al, 1992). Furthermore, radiolabeled FGF2 binds to PGCs in culture, suggesting the presence of FGF receptors (FGFRs) (Resnick et al, 1998). However, the FGFR combinations expressed by germ cells, the ligands they respond to, and their individual or collective roles in germ cell behavior are not known.…”

Culture of Rabbit Embryonic Germ Cells Derived from Primordial Germ Cells

“…The forming rate of PGCsderived colonies from 19 dpc and 20 dpc was higher than other periods (Pe0.05). Although the establishment of mouse ES cell lines is independent of strains, ES cell lines derived from different origins varied in their growth mode and dependence on feeder layers (Resnick et al, 1998). Mouse ES-like cells have already been derived from many different strains but ES cell lines derived from the 129 strain mouse is better than others as a transgenic vector.…”

“…If PGCs are cultured with stem cell factor (SCF), leukemia inhibitory factor (LIF), they can form permanent cell lines, termed embryonic germ (EG) cells. EG cells share many properties with embryonic stem (ES) cells including the ability to colonize the germ line (Resnick et al, 1998).…”