Functional analysis of genes required for germline-stem-cell niche formation in Drosophila ovary

成体组织中的干细胞是由一种特殊的微环境维持的，这种微环境被称为“生态位”，它产生维持干细胞规格和功能的信号。然而，在器官发生过程中，干细胞命运和生态位细胞命运是如何最初确定的，这在很大程度上是未知的。我们以果蝇卵巢为模型系统，研究了干细胞和小生境细胞命运决定的调控机制。在果蝇卵巢中，生殖系干细胞（GSCs）和生态位细胞分别由卵巢中的原始生殖细胞（PGCs）和体细胞亚群转化为幼虫-蛹形成。我们之前对原始生殖细胞的谱系分析表明，胚胎性腺前半部分的PGCs经常与晚期幼虫卵巢的新生生态位细胞接触，并在成年卵巢中产生GSCs。这表明GSC的命运在幼虫-蛹转变之前就已经确定了，可能在胚胎性腺中。表达一个特定的生态位细胞增强陷阱标记表明，生态位细胞可能起源于胚胎性腺的前部。在这里，我们筛选出一个新的基因，该基因表达体细胞性腺前体，与性腺前半部分的PGCs接触，并编码一个跨膜蛋白。胚胎GSCs的基因敲除及其零突变导致成年卵巢中GSCs的缺失或减少。这些结果表明，GSC命运的决定涉及胚胎性腺前半部分SGP/PGC的相互作用。我们还筛选出了三个候选基因，这些基因参与了生态位细胞的形成和/或分化。

Stem cells in the adult tissue are maintained by a special microenvironment called "niche", which produces signals that maintain stem cell specification and function. However, how stem-cell fate and niche-cell fate are initially established during organogenesis is largely unknown. We have studied regulation mechanisms underlying stem-cell and niche-cell fate determination using Drosophila ovary as a model system. In the Drosophila ovary, germline stem cells (GSCs) and niche cells are formed by larval-pupal transition from a subset of primordial germ cells (PGCs) and somatic cells in the ovary, respectively. Previous our lineage analysis of primordial germ cell showed that PGCs in the anterior half of the embryonic gonad frequently acquired contact with nascent niche cells in the late larval ovary and gave rise to GSCs in the adult ovary. This suggests that the GSC fate is predetermined before larval-pupal transition, possibly in the embryonic gonads, Expression of a niche-cell specific enhancer-trap marker suggested that niche cells may originate from anterior portion of embryonic somatic gonads. Here, we screened out one novel gene which is expressed somatic gonadal precursors contacting the PGCs in the anterior half of the gonads and encode a transmembrane protein. Gene knock-down in the embryonic SGPs and its null mutation resulted in the absence or decrease of GSCs in the adult ovaries. These results suggest that GSC fate determination involves SGP/PGC interaction in the anterior half of the embryonic gonad. We also screened out three candidate genes which are involved in niche cell formation and/or differentiation.