The Drosophila adult midgut is a model epithelial tissue composed of a few major cell types with distinct regional identities. One of the limitations to its analysis is the lack of tools to manipulate gene expression based on these regional identities. To overcome this obstacle, we applied the intersectional split-GAL4 system to the adult midgut and report 653 driver combinations that label cells by region and cell type. We first identified 424 split-GAL4 drivers with midgut expression from over 7,300 drivers screened, and then evaluated the expression patterns of each of these 424 when paired with three reference drivers that report activity specifically in progenitor cells, enteroendocrine cells, or enterocytes. We also evaluated a subset of the drivers expressed in progenitor cells for expression in enteroblasts using another reference driver. We show that driver combinations can define novel cell populations by identifying a driver that marks a distinct subset of enteroendocrine cells expressing genes usually associated with progenitor cells. The regional cell type patterns associated with the entire set of driver combinations are documented in a freely available website, providing information for the design of thousands of additional driver combinations to experimentally manipulate small subsets of intestinal cells. In addition, we show that intestinal enhancers identified with the split-GAL4 system can confer equivalent expression patterns on other transgenic reporters. Altogether, the resource reported here will enable more precisely targeted gene expression for studying intestinal processes, epithelial cell functions, and diseases affecting self-renewing tissues.

中文翻译：

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鉴定允许对果蝇肠道进行区域细胞类型操纵的 Split-GAL4 驱动程序和增强子。

果蝇成体中肠是一种模型上皮组织，由几种具有不同区域特征的主要细胞类型组成。其分析的局限性之一是缺乏根据这些区域特征操纵基因表达的工具。为了克服这一障碍，我们将交叉 split-GAL4 系统应用于成人中肠，并报告了 653 个驱动程序组合，按区域和细胞类型标记细胞。我们首先从筛选的 7,300 多个驱动程序中鉴定出具有中肠表达的 424 个 split-GAL4 驱动程序，然后在与报告祖细胞、肠内分泌细胞或肠上皮细胞特异性活动的三个参考驱动程序配对时，评估了这 424 个中每一个的表达模式。我们还使用另一个参考驱动程序评估了祖细胞中表达的驱动程序子集在成肠细胞中的表达。我们表明，驱动程序组合可以通过识别驱动程序来定义新的细胞群，该驱动程序标记了表达通常与祖细胞相关的基因的肠内分泌细胞的独特子集。与整套驱动程序组合相关的区域细胞类型模式记录在一个免费网站中，为设计数千个附加驱动程序组合以实验性地操纵肠道细胞的小子集提供信息。此外，我们表明用 split-GAL4 系统鉴定的肠道增强子可以赋予其他转基因报告基因相同的表达模式。总而言之，这里报告的资源将使更精确的目标基因表达成为可能，用于研究肠道过程、上皮细胞功能和影响自我更新组织的疾病。