RNA-binding protein TIAR is essential for primordial germ cell development
RNA-binding protein TIAR is essential for primordial germ cell development
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DOI：
10.1073/pnas.95.5.2331
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发表时间：
1998-03-03
影响因子：
11.1
通讯作者：
Streuli, M
中科院分区：
文献类型：
--
作者：
Beck, ARP;Miller, IJ;Streuli, M
原始生殖细胞（PGCs）通过复杂的成熟过程产生卵子和精子，这些过程需要细胞迁移和增殖，然而，在PGC发育的早期阶段，对控制配子形成的基因知之甚少，尽管已知几种突变会严重减少到达和填充生殖嵴的PGCs的数量，但这些基因中只有两种的分子身份是已知的：c-kit受体蛋白酪氨酸激酶和c-kit配体在此，我们报道了缺乏TIAR（一种在PGCs中高度表达的RNA识别基序/核糖核蛋白型RNA结合蛋白）的突变小鼠不能发育精原细胞或卵原细胞，这种发育缺陷是胚胎11.5天左右迁移到生殖嵴的PGCs存活减少的结果。（E11.5），与野生型胚胎相比，在E11.5时TIAR缺陷型胚胎中生殖嵴中的PGCs数量严重减少，而在E13.5时突变体中完全不存在PGCs。此外，TIAR缺陷型胚胎干细胞在体外甲基纤维素培养试验中在不存在外源性白血病抑制因子的情况下不增殖，支持TIAR在调节细胞增殖中的作用。由于PGC的发育依赖于几种生长因子的作用，这些结果与TIAR在PGC发育所必需的存活因子或存活因子受体的表达中的作用一致，因此TIAR缺陷小鼠提供了研究PGC发育的分子机制的模型系统，并且可能是某些形式的特发性不育的基础。
Primordial germ cells (PGCs) give rise to both eggs and sperm via complex maturational processes that require both cell migration and proliferation, However, little is known about the genes controlling gamete formation during the early stages of PGC development, Although several mutations are known to severely reduce the number of PGCs reaching and populating the genital ridges, the molecular identity of only two of these genes is known: the c-kit receptor protein tyrosine kinase and the c-kit ligand (the steel factor), Herein, we report that mutant mice lacking TIAR, an RNA recognition motif/ribonucleoprotein-type RNA-binding protein highly expressed in PGCs, fail to develop spermatogonia or oogonia, This developmental defect is a consequence of reduced survival of PGCs that migrate to the genital ridge around embryonic day 11.5 (E11.5), The numbers of PGCs populating the genital ridge in TIAR-deficient embryos are severely reduced compared to wild-type embryos by E11.5 and in the mutants PGCs are completely absent at E13.5. Furthermore, TIAR-deficient embryonic stem cells do not proliferate in the absence of exogenous leukemia inhibitory factor in an in vitro methylcellulose culture assay, supporting a role for TIAR in regulating cell proliferation. Because the development of PGCs relies on the action of several growth factors, these results are consistent with a role for TIAR in the expression of a survival factor or survival factor receptor that is essential for PGC development, TIAR-deficient mice thus provide a model system to study molecular mechanisms of PGC development and possibly the basis for some forms of idiopathic infertility.