Role of leukemia inhibitory factor and its receptor in mouse primordial germ cell growth.
The pleiotropic cytokine leukemia inhibitory factor (LIF) is able to promote the growth of mouse primordial germ cells (PGCs) in culture. It is unclear whether LIF acts directly on PGCs or indirectly via feeder cells or embryonic somatic cells. To understand the role of LIF in PGC growth, we have carried out molecular and cell culture analyses to investigate the role of both the LIF ligand and its receptor in PGC development. LIF is able to stimulate PGC growth independently of the presence of feeder cells supporting the hypothesis that LIF acts directly on PGCs to promote their growth. We show here that transcripts for the low-affinity LIF receptor (LIFR), an integral component of the functional LIF receptor complex, are expressed in the developing gonad. Fluorescence-activated cell sorter (FACS) analysis, using an anti-LIFR antiserum, demonstrates that LIFR is present on the surface of PGCs, suggesting that PGCs are likely to be a direct target of LIF action in culture. Signalling via LIFR is essential for PGC growth in culture since the anti-LIFR antiserum, which blocks LIF binding to its receptor, abolishes PGC survival in culture. Two LIF-related cytokines, namely oncostatin M and ciliary neurotrophic factor, can also promote PGC growth in culture in addition to LIF. Thus one or more of these LIFR-dependent cytokines may play an important role in PGC development in mice.
Cheng
L
L
ABL-Basic Research Program, NCI-FCRDC, Frederick, Maryland 21702-1201.
Gearing
D P
DP
White
L S
LS
Compton
D L
DL
Schooley
K
K
Donovan
P J
PJ
D000818:Animals; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor; D016207:Cytokines / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D005854:Germ Cells / Q000166:cytology / Q000254:growth & development*; D006131:Growth Inhibitors / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins / Q000502:physiology; D053683:Oncostatin M; D010455:Peptides / Q000502:physiology; D018121:Receptors, Cytokine / Q000502:physiology*; D053606:Receptors, OSM-LIF
D020934:Ciliary Neurotrophic Factor; D016207:Cytokines; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507838:Lif protein, mouse; C507841:Lifr protein, mouse; D008222:Lymphokines; D009419:Nerve Tissue Proteins; C508352:Osm protein, mouse; D010455:Peptides; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D016222:Fibroblast Growth Factor 2; D053683:Oncostatin M