A genome-scale in vivo RNAi analysis of epithelial development in Drosophila identifies new proliferation domains outside of the stem cell niche
A genome-scale in vivo RNAi analysis of epithelial development in Drosophila identifies new proliferation domains outside of the stem cell niche
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DOI：
10.1242/jcs.144519
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发表时间：
2014-06-15
影响因子：
4
通讯作者：
Riechmann, Veit
中科院分区：
文献类型：
--
作者：
Berns, Nicola;Woichansky, Innokenty;Riechmann, Veit
果蝇卵子发生系统为研究上皮组织的发育提供了极好的模型。在这里，我们报告了第一个基因组规模的体内RNA干扰（RNAi）筛选控制上皮发育的基因。通过直接分析细胞和组织结构，我们确定了1125个基因，并将其分配给上皮形成和稳态中的七种不同功能。我们通过产生Vps60的突变体来验证我们的筛选的意义，Vps60是运输（ESCRT）机制所需的内体分选复合物的一个组分。这一分析为滤泡上皮细胞增殖的时空控制提供了新的见解。之前的研究已经确定了控制毛囊干细胞龛分裂的信号。然而，99%的细胞分裂发生在小生境之外，目前还不清楚这些分裂是如何控制的。我们的数据区分了干细胞小生境之外的两个新领域，其中对增殖有不同的控制。一个结构域邻接小生境，其特征在于ESCRT、Notch和JAK/STAT介导的增殖控制。与该结构域相邻，另一个结构域被定义为ESCRT对细胞分裂的影响的丧失。因此，在发育过程中，上皮细胞通过各种微环境，发挥不同的增殖控制模式。这些模式之间的转换可能反映了上皮细胞随时间推移的“干性”下降。
The Drosophila oogenesis system provides an excellent model to study the development of epithelial tissues. Here, we report the first genome-scale in vivo RNA interference (RNAi) screen for genes controlling epithelial development. By directly analysing cell and tissue architecture we identified 1125 genes, which we assigned to seven different functions in epithelial formation and homeostasis. We validated the significance of our screen by generating mutants for Vps60, a component of the endosomal sorting complexes required for transport (ESCRT) machinery. This analysis provided new insights into spatiotemporal control of cell proliferation in the follicular epithelium. Previous studies have identified signals controlling divisions in the follicle stem cell niche. However, 99% of cell divisions occur outside of the niche and it is unclear how these divisions are controlled. Our data distinguish two new domains outside of the stem cell niche where there are differing controls on proliferation. One domain abuts the niche and is characterised by ESCRT, Notch and JAK/STAT-mediated control of proliferation. Adjacent to this domain, another domain is defined by loss of the impact of ESCRT on cell division. Thus, during development epithelial cells pass through a variety of micro-environments that exert different modes of proliferation control. The switch between these modes might reflect a decrease in the 'stemness' of epithelial cells over time.