Donovan P J
Mammalian Genetics Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702.
Curr Top Dev Biol. 1994;29:189-225. doi: 10.1016/s0070-2153(08)60551-7.
This chapter focused on three key regulators of PGC survival and proliferation; SLF, LIF, and bFGF. The survival of all animal cells may require multiple polypeptide factors and PGCs seem to be no exception (Fig. 7). A number of lines of evidence suggest that membrane-bound forms of SLF may be required for PGC survival. These data suggest an exquisite mechanism for controlling both PGC survival and migration. Thus PGCs that stray from the normal migratory pathway might be eliminated through programmed cell death. SLF, together with LIF, can stimulate PGC proliferation in culture and it seems likely that LIF or a related cytokine may function in vivo to regulate PGC survival and proliferation. Animals doubly deficient in LIF and its relatives may soon allow the roles of these cytokines in PGC development to be determined. Although bFGF is a potent PGC mitogen in vitro, whether PGCs ever encounter bFGF in vivo remains questionable since in culture it alters both the proliferative and developmental potential of PGCs. TGF beta or MIS may be important negative regulators of PGC development, and mice lacking these factors should allow their role in PGC development to be assessed.
本章重点关注原始生殖细胞(PGC)存活和增殖的三个关键调节因子:干细胞因子(SLF)、白血病抑制因子(LIF)和碱性成纤维细胞生长因子(bFGF)。所有动物细胞的存活可能都需要多种多肽因子,原始生殖细胞似乎也不例外(图7)。多项证据表明,原始生殖细胞的存活可能需要膜结合形式的干细胞因子。这些数据提示了一种控制原始生殖细胞存活和迁移的精妙机制。因此,偏离正常迁移途径的原始生殖细胞可能会通过程序性细胞死亡被清除。干细胞因子与白血病抑制因子一起,可在体外刺激原始生殖细胞增殖,白血病抑制因子或相关细胞因子很可能在体内发挥作用,调节原始生殖细胞的存活和增殖。同时缺乏白血病抑制因子及其相关因子的动物,可能很快就能确定这些细胞因子在原始生殖细胞发育中的作用。虽然碱性成纤维细胞生长因子在体外是一种有效的原始生殖细胞促有丝分裂原,但原始生殖细胞在体内是否会接触到碱性成纤维细胞生长因子仍值得怀疑,因为在培养中它会改变原始生殖细胞的增殖和发育潜能。转化生长因子β(TGF beta)或苗勒管抑制物质(MIS)可能是原始生殖细胞发育的重要负调节因子,缺乏这些因子的小鼠应能用于评估它们在原始生殖细胞发育中的作用。