AIP1-mediated actin disassembly is required for postnatal germ cell migration and spermatogonial stem cell niche establishment.
AIP1-mediated actin disassembly is required for postnatal germ cell migration and spermatogonial stem cell niche establishment.
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AIP1 介导的肌动蛋白分解是出生后生殖细胞迁移和精原干细胞生态位建立所必需的
DOI：
10.1038/cddis.2015.182
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发表时间：
2015-07-16
影响因子：
9
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Xu J;Wan P;Wang M;Zhang J;Gao X;Hu B;Han J;Chen L;Sun K;Wu J;Wu X;Huang X;Chen J
在哺乳动物中，精原干细胞(SSCs)起源于称为性腺细胞的早期生殖细胞，性腺细胞在胚胎发育期间来自原始生殖细胞，直到出生时一直保持静止。出生后，这些生殖细胞从睾丸索中心，通过支持细胞，向基底膜迁移，形成SSC池，建立SSC生态位结构。然而，生殖细胞迁移和生态位建立的分子机制在很大程度上是未知的。在这里，我们证明了肌动蛋白拆解因子肌动蛋白相互作用蛋白1(AIP1)在生殖细胞和支持细胞中都是调节这一过程所必需的。生殖细胞特异性或支持细胞特异性Aip1基因的缺失均导致出生后4天或5天后生殖细胞迁移明显缺陷，并伴随着受影响细胞中肌动蛋白细丝(F-肌动蛋白)水平的升高。此外，我们的数据表明，生殖细胞和支持细胞之间的相互作用，可能是通过E-钙粘附素介导的细胞黏附，是生殖细胞向基底膜迁移的关键。最后，Sertoli细胞中Aip1的缺失减少了SSC的自我更新，促进了精原细胞的分化，但不影响生长因子的表达和分泌水平，提示SSC功能的中断是由于出生后壁龛的结构变化所致。
In mammals, spermatogonial stem cells (SSCs) arise from early germ cells called gonocytes, which are derived from primordial germ cells during embryogenesis and remain quiescent until birth. After birth, these germ cells migrate from the center of testicular cord, through Sertoli cells, and toward the basement membrane to form the SSC pool and establish the SSC niche architecture. However, molecular mechanisms underlying germ cell migration and niche establishment are largely unknown. Here, we show that the actin disassembly factor actin interacting protein 1 (AIP1) is required in both germ cells and Sertoli cells to regulate this process. Germ cell-specific or Sertoli cell-specific deletion of Aip1 gene each led to significant defects in germ cell migration after postnatal day 4 or 5, accompanied by elevated levels of actin filaments (F-actin) in the affected cells. Furthermore, our data demonstrated that interaction between germ cells and Sertoli cells, likely through E-cadherin-mediated cell adhesion, is critical for germ cells’ migration toward the basement membrane. At last, Aip1 deletion in Sertoli cells decreased SSC self-renewal, increased spermatogonial differentiation, but did not affect the expression and secretion levels of growth factors, suggesting that the disruption of SSC function results from architectural changes in the postnatal niche.