ROLE OF LEUKEMIA INHIBITORY FACTOR AND ITS RECEPTOR IN MOUSE PRIMORDIAL GERM-CELL GROWTH

The pleiotropic cytokine leukemia inhibitory factor (LIF) is able to p romote 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 PG C growth, we have carried out molecular and cell culture analyses to i nvestigate the role of both the LIF ligand and its receptor in PGC dev elopment. LIF is able to stimulate PGC growth independently of the pre sence of feeder cells supporting the hypothesis that LIF acts directly on PGCs to promote their growth. We show here that transcripts for th e low-affinity LIF receptor (LIFR), an integral component of the funct ional LIF receptor complex, are expressed in the developing gonad. Flu orescence-activated cell sorter (FACS) analysis, using an anti-LIFR an tiserum, demonstrates that LIFR is present on the surface of PGCs, sug gesting that PGCs are likely to be a direct target of LIF action in cu lture. Signalling via LIFR is essential for PGC growth in culture sinc e the anti-LIFR antiserum, which blocks LIF binding to its receptor, a bolishes PGC survival in culture. Two LIF-related cytokines, namely on costatin M and ciliary neurotrophic factor, can also promote PGC growt h in culture in addition to LIF. Thus one or more of these LIFR-depend ent cytokines may play an important role in PGC development in mice.