Analysis of hypomorphic Kitlsl mutants suggests different requirements for KITL in proliferation and migration of mouse primordial germ cells
Analysis of hypomorphic Kitlsl mutants suggests different requirements for KITL in proliferation and migration of mouse primordial germ cells
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DOI：
10.1095/biolreprod.105.042846
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发表时间：
2005-10-01
影响因子：
3.6
通讯作者：
Bedell, MA
中科院分区：
文献类型：
--
作者：
Zama, AM;Hudson, FP;Bedell, MA
小鼠生殖细胞的发育是在原肠胚形成过程中从体细胞中分离出少量原始生殖细胞（PGCs）后开始的。在随后的4 ~ 5天内，PGCs进入后肠，从后肠定向迁移到发育中的性腺，细胞数量大量增加。Kit配体（KITL，又称干细胞因子和肥大细胞生长因子）是PGCs存活和增殖所必需的。然而，很少有关于KITL在PGC迁移中的直接作用的信息。通过比较多个Kid突变的影响，包括两个n -乙基-n -亚硝基源诱导的亚形态突变，我们能够区分PGC发展的阶段，哪些阶段优先受到某些突变的影响。我们提供的证据表明，在PGC开始迁移之前和之后，KITL在增殖中的需求是不同的，并且需要不同水平的KITL功能来支持PGC的增殖和迁移。这项研究说明了等位基因系列突变对解剖发育过程的有用性，并表明这些突变可能有助于进一步研究KITL在配子体发生中的分子机制。
Germ cell development in mice is initiated when a small number of primordial germ cells (PGCs) are set aside from somatic cells during gastrulation. In the subsequent 4 to 5 days, PGCs enter the hindgut, undergo a directed migration away from the hindgut into the developing gonads, and undergo a massive increase in cell number. It is well established that Kit ligand (KITL, also known as stem cell factor and mast cell growth factor) is required for the survival and proliferation of PGCs. However, there is little information on a direct role for KITL in PGC migration. By comparing the effects of multiple Kid mutations, including two N-ethyl-N-nitrosourea-induced hypomorphic mutations, we were able to distinguish stages of PGC development that are preferentially affected by certain mutations. We provide evidence that the requirements for KITL in proliferation are different in PGCs before and after they start migrating, and different levels of KITL function are required to support PGC proliferation and migration. This study illustrates the usefulness of an allelic series of mutations to dissect developmental processes and suggests that these mutants may be useful for further studies of molecular mechanisms of KITL functions in gametogenesis.