Cell type-autonomous and non-autonomous requirements for Dmrt1 in postnatal testis differentiation
Cell type-autonomous and non-autonomous requirements for Dmrt1 in postnatal testis differentiation
复制标题
DOI：
10.1016/j.ydbio.2007.04.046
复制
发表时间：
2007-07-15
影响因子：
2.7
通讯作者：
Zarkower, David
中科院分区：
文献类型：
--
作者：
Kim, Shinseog;Bardwell, Vivian J.;Zarkower, David
含有DM结构域的基因调节多个门的性别分化。DM结构域是一种保守的DNA结合基序，最先在果蝇和秀丽线虫的双性性中发现。DM域基因DMRT1是脊椎动物睾丸分化所必需的。在小鼠中，DMRT1在减数分裂前的生殖细胞和支持细胞中表达，这为精子发生提供了必要的支持。DMRT1缺失突变小鼠有严重的发育不良睾丸，生后支持细胞和生殖细胞都不能正常分化。在这里，我们使用条件基因打靶来确定DMRT1在每种细胞类型中的功能。我们发现DMRT1在支持细胞的出生后分化、生殖系维持和减数分裂进程中是必需的。生殖细胞需要DMRT1来径向迁移到生精小管的外围，在那里将形成生精龛，重新激活有丝分裂，并在出生后第一周后存活。因此，DMRT1活性在支持细胞和生殖细胞谱系中是自主需要的，而支持细胞中的DMRT1活性也是维持生殖系的非自主需要。这些结果表明，DMRT1在控制幼年睾丸的重塑和分化中起着多方面的作用。(C)2007 Elsevier Inc.保留所有权利。
Genes containing the DM domain, a conserved DNA binding motif first found in Doublesex of Drosophila and mab-3 of Caenorhabditis elegans, regulate sexual differentiation in multiple phyla. The DM domain gene Dmrt1 is essential for testicular differentiation in vertebrates. In the mouse, Dmrt1 is expressed in pre-meiotic germ cells and in Sertoli cells, which provide essential support for spermatogenesis. Dmrt1 null mutant mice have severely dysgenic testes in which Sertoli cells and germ cells both fail to differentiate properly after birth. Here we use conditional gene targeting to identify the functions of Dmrt1 in each cell type. We find that Dmrt1 is required in Sertoli cells for their postnatal differentiation, and for germ line maintenance and for meiotic progression. Dmrt1 is required in germ cells for their radial migration to the periphery of the seminiferous tubule where the spermatogenic niche will form, for mitotic reactivation and for survival beyond the first postnatal week. Thus Dmrt1 activity is required autonomously in the Sertoli and germ cell lineages, and Dmrt1 activity in Sertoli cells is also required nonautonomously to maintain the germ line. These results demonstrate that Dmrt1 plays multiple roles in controlling the remodeling and differentiation of the juvenile testis. (c) 2007 Elsevier Inc. All rights reserved.