Department of Developmental Genetics, DKFZ-ZMBH Allianz, INF 581, Heidelberg 69120, Germany.
Cell Res. 2009 Oct;19(10):1139-49. doi: 10.1038/cr.2009.71. Epub 2009 Jun 23.
Gonad development requires a coordinated soma-germline interaction that ensures renewal and differentiation of germline and somatic stem cells to ultimately produce mature gametes. The Drosophila tumour suppressor gene discs large (dlg) encodes a septate junction protein functioning during epithelial polarization, asymmetric neuroblast division, and formation of neuromuscular junctions. Here, we report the role of dlg in testis development and its critical function in somatic cyst cells (SCCs). In these cells dlg is primarily required for their survival and expansion, and contributes to spermatocyte cyst differentiation. Cell death primarily occurred in SCCs at the end of spermatogonial amplification at a time when Dlg becomes restricted in wild-type (wt) testes to the distal somatic cells capping the growing spermatocyte cysts. RNAi depletion of dlg transcripts in early SCCs fully prevented testis development, whereas depletion in late SCCs resulted in a breakdown of spermatocyte cyst structure and germ cell individualization. Specific dlg expression in SCCs resulted in developmental rescue of dlg mutant testes, whereas its expression in germ cells exerted no such effect. dlg overexpression in wt testes led to spermatocyte cyst expansion at the expense of spermatogonial cysts. Our data demonstrate that dlg is essentially required in SCCs for their survival, expansion, and differentiation, and for the encapsulation of the germline cells.
生殖腺的发育需要协调的体-生殖细胞相互作用,以确保生殖细胞和体干细胞的更新和分化,最终产生成熟的配子。果蝇肿瘤抑制基因 discs large (dlg) 编码了一种隔膜连接蛋白,在上皮极化、不对称神经母细胞分裂和形成神经肌肉接头的过程中发挥作用。在这里,我们报告了 dlg 在睾丸发育中的作用及其在体细胞小腔细胞(SCCs)中的关键功能。在这些细胞中,dlg 主要是它们存活和扩张所必需的,并有助于精母细胞小腔的分化。细胞死亡主要发生在精原细胞扩增末期,此时 Dlg 在野生型(wt)睾丸中局限于远端体细胞,覆盖正在生长的精母细胞小腔。早期 SCCs 中 dlg 转录本的 RNAi 耗竭完全阻止了睾丸发育,而晚期 SCCs 中的耗竭导致精母细胞小腔结构和生殖细胞个体化的破坏。SCCs 中特异性表达 dlg 导致 dlg 突变体睾丸的发育挽救,而在生殖细胞中表达则没有这种效果。wt 睾丸中 dlg 的过表达导致精母细胞小腔的扩张,而以精原细胞小腔为代价。我们的数据表明,dlg 在 SCCs 中对于它们的存活、扩张和分化以及生殖细胞的包裹是必不可少的。