Wt1不仅在睾丸的体细胞谱系发育中发挥作用，还在生殖细胞的发育中发挥作用。

Wt1 functions in the development of germ cells in addition to somatic cell lineages of the testis.

作者信息

Natoli Thomas A, Alberta Julia A, Bortvin Alex, Taglienti Mary E, Menke Douglas B, Loring Jan, Jaenisch Rudolf, Page David C, Housman David E, Kreidberg Jordan A

机构信息

Department of Medicine, The Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.

出版信息

Dev Biol. 2004 Apr 15;268(2):429-40. doi: 10.1016/j.ydbio.2003.12.033.

DOI:10.1016/j.ydbio.2003.12.033

PMID:15063178

Abstract

The Wilms' tumor suppressor gene, Wt1, encodes a transcription factor critical for development of the urogenital system. To identify lineages within the developing urogenital system that have a cell-autonomous requirement for Wt1, chimeric mice were generated from Wt1-null ES cells. Males with large contributions of Wt1-/- cells showed hypoplastic and dysgenic testes, with seminiferous tubules lacking spermatogonia. Wt1-null cells contributed poorly to both somatic and germ cell lineages within the developing gonad, suggesting an unexpected role for Wt1 in germ cell development in addition to a role in the development of the somatic lineages of the gonad. Wt1 expression was detected in embryonic germ cells beginning at embryonic day 11.5 after migrating primordial germ cells (PGCs) have entered the gonad. Germ cells isolated from Wt1-null embryos showed impaired growth in culture, further demonstrating a role for Wt1 in germ cell proliferation or survival. Therefore, Wt1 plays important, and in some cases previously unrecognized, roles in multiple lineages during urogenital development.

摘要

威尔姆斯瘤抑制基因Wt1编码一种对泌尿生殖系统发育至关重要的转录因子。为了确定发育中的泌尿生殖系统内对Wt1有细胞自主需求的细胞谱系，利用Wt1基因敲除的胚胎干细胞生成了嵌合小鼠。Wt1-/-细胞贡献比例大的雄性小鼠睾丸发育不全且发育异常，生精小管中缺乏精原细胞。Wt1基因敲除的细胞对发育中的性腺内的体细胞和生殖细胞谱系的贡献都很少，这表明Wt1除了在性腺体细胞谱系发育中发挥作用外，在生殖细胞发育中也发挥了意想不到的作用。在迁移的原始生殖细胞（PGC）进入性腺后的胚胎第11.5天开始，在胚胎生殖细胞中检测到Wt1表达。从Wt1基因敲除胚胎中分离出的生殖细胞在培养中生长受损，进一步证明了Wt1在生殖细胞增殖或存活中的作用。因此，Wt1在泌尿生殖系统发育过程中的多个细胞谱系中发挥着重要作用，在某些情况下这些作用以前未被认识到。