A RECEPTOR TYROSINE KINASE SKY AND ITS LIGAND GAS 6 ARE EXPRESSED IN GONADS AND SUPPORT PRIMORDIAL GERM CELL GROWTH OR SURVIVAL IN CULTURE

摘要

Growth and survival of germ cells seem to be strictly regulated by a number of environmental and intrinsic factors. One of the most important factor is Steel factor, which is necessary not only for the rapid proliferation and survival of primordial germ cells(PGCs) in embryos, but also for the development of spermatogonia and oocytes in adult gonads. Other growth factors including leukemia inhibitory factor(LIF), basic fibroblast growth factor(bFGF) and tumor necrosis factor α(TNFα) synergisticallypromote PGC growth in culture. In addition, pituitary adenylate cyclase-activating polypeptide(PACAP) which increases intracellular cAMP in PGCs and retinoic acids also stimulate their proliferation. In contrast, TGFβ1 kihibits PGC growth in culture. Binding of these factors to their specific receptors activates different intracellular signaling molecules. For example, receptor tyrosine kinase, c-Kit associates PI3 kinase and phospholipase Cγ 1. LIF receptor which comprises ligand biding subunit andsignal transducer, gp130, interacts with Jak-Tyk kinase. Therefore, synergistic action of different signal transduction pathway seems to be important for PGC growth and survival. In W and Steel mutant mice which lack c-kit and Steel factor gene respectively, growth and survival of PGCs are impaired and this clearly shows the gene products are physiologically important for PGCs. However, the functions of other factors on PGCs in vivo are not clear so far. For example, PGCs in mice lacking LIF and LIFR gene are normal. In this case, ligands and/or ligand binding subunits 0f receptors may be redundant, because gp130 is also a component of receptors for Oncostatin M and ciliary neurotropic factor(CNTF), and they enhance PGC growth in culture. It is also likely that unknown factors are physiological regulators of PGC growth.