In addition to performing digestion and nutrient absorption, the intestine serves as one of the first barriers to the external environment, crucial for protecting the host from environmental toxins, pathogenic invaders, and other stress inducers. The gene regulatory network (GRN) governing embryonic development of the endoderm and subsequent differentiation and maintenance of the intestine has been well-documented in C. elegans. A key regulatory input that initiates activation of the embryonic GRN for endoderm and mesoderm in this animal is the maternally provided SKN-1 transcription factor, an ortholog of the vertebrate Nrf1 and 2, which, like C. elegans SKN-1, perform conserved regulatory roles in mediating a variety of stress responses across metazoan phylogeny. Other key regulatory factors in early gut development also participate in stress response as well as in innate immunity and aging and longevity. In this review, we discuss the intersection between genetic nodes that mediate endoderm/intestine differentiation and regulation of stress and homeostasis. We also consider how direct signaling from the intestine to the germline, in some cases involving SKN-1, facilitates heritable epigenetic changes, allowing transmission of adaptive stress responses across multiple generations. These connections between regulation of endoderm/intestine development and stress response mechanisms suggest that varying selective pressure exerted on the stress response pathways may influence the architecture of the endoderm GRN, thereby leading to genetic and epigenetic variation in early embryonic GRN regulatory events.

除了进行消化和营养吸收外，肠还成为外部环境的第一道屏障，对于保护宿主免受环境毒素，病原体入侵者和其他压力诱导物的侵害至关重要。在秀丽隐杆线虫中已经充分证明了控制内胚层胚胎发育以及随后的肠道分化和维持的基因调控网络（GRN）。由母体提供的SKN-1转录因子是脊椎动物Nrf1和2的直系同源物，就像线虫一样，这是启动该动物内胚层和中胚层胚胎GRN活化的关键调控输入。SKN-1在介导后生系统发育的各种应激反应中发挥保守的调节作用。肠道早期发育中的其他关键调控因素也参与应激反应以及先天免疫，衰老和长寿。在这篇综述中，我们讨论了介导内胚层/肠道分化的遗传节点与压力和动态平衡调节之间的交集。我们还考虑了从肠到种系的直接信号传导（在某些情况下涉及SKN-1）如何促进可遗传的表观遗传学变化，从而允许适应性应激反应跨多个世代传播。