GLI1 localization in the germinal epithelial cells alternates between cytoplasm and nucleus: Upregulation in transgenic mice blocks spermatogenesis in pachytene
GLI1 localization in the germinal epithelial cells alternates between cytoplasm and nucleus: Upregulation in transgenic mice blocks spermatogenesis in pachytene
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DOI：
10.1095/biolreprod65.6.1663
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发表时间：
2001-12-01
影响因子：
3.6
通讯作者：
Goldberg, E
中科院分区：
文献类型：
--
作者：
Kroft, TL;Patterson, J;Goldberg, E
锌指转录因子 GLI1 是 Hedgehog (Hh) 家族成员信号传导的介体。雄性小鼠的睾丸支持细胞中表达的 Hh 同源物 Desert Hedgehog (Dhh) 被敲除后是不育的，这表明 Dhh/GLI1 通路在精子发生中发挥作用。使用针对人 GLI1 的抗血清，我们发现在第一轮精子发生过程中，GLI1 表达最初在细胞质中，然后转移到支持细胞和生殖细胞的细胞核，最后转移回细胞质。在成年小鼠睾丸中，GLI1 表达定位于生殖细胞的细胞核，从粗线期细胞开始，一直持续到圆形精子细胞。 GLI1 在伸长的精子细胞中的定位从细胞核转移到细胞质，并与微管相关。我们还检查了一系列过度表达人类 GLI1 的转基因小鼠。该品系中的雄性小鼠是不育的。精子发生在粗线期阶段被阻断，并且形态上无法区分的粗线期细胞的子集经历了凋亡。 Patched-2（一种 Dhh 受体）和 Fused（信号转导途径的另一个组成部分）在 Leydig 细胞以及初级和次级精母细胞中表达。 GLI1 在与 Patched-2 和 Fused 相同的细胞类型中表达，以及 GLI1 过表达对精子发生的破坏表明，GLI1 是睾丸中 Dhh 信号的介体，并且它可能是精子发生的调节剂。
The zinc finger transcription factor GLI1 is the mediator of signaling by members of the Hedgehog (Hh) family. Male mice in which Desert hedgehog (Dhh), an Hh homologue expressed in Sertoli cells of the testis, was knocked out are sterile, suggesting that the Dhh/GLI1 pathway plays a role in spermatogenesis. Using an antiserum raised against human GLI1, we found that during the first round of spermatogenesis, GLI1 expression is initially cytoplasmic, then shifts to the nuclei of Sertoli and germ cells, and finally shifts back to the cytoplasm. in the adult mouse testis, GLI1 expression localized to the nuclei of germ cells, beginning with pachytene cells and persisting through round spermatids. Localization of GLI1 in elongating spermatids shifted from the nucleus to the cytoplasm and became associated with microtubules. We also examined a line of transgenic mice that overexpressed human GLI1. Male mice in this line were sterile. Spermatogenesis was blocked at the pachytene stage, and a subset of the morphologically indistinguishable pachytene cells underwent apoptosis. Patched-2, which is a Dhh receptor, and Fused, another component of the signal transduction pathway, are expressed in Leydig cells and in primary and secondary spermatocytes. Expression of GLI1 in the same cell types as Patched-2 and Fused and the disruption of spermatogenesis by GLI1 overexpression suggest that GLI1 is the mediator of the Dhh signal in the testis, and that it may be a regulator of spermatogenesis.