Troll Joshua V, Hamilton M Kristina, Abel Melissa L, Ganz Julia, Bates Jennifer M, Stephens W Zac, Melancon Ellie, van der Vaart Michiel, Meijer Annemarie H, Distel Martin, Eisen Judith S, Guillemin Karen
Institute of Molecular Biology, Department of Biology, 1229 University of Oregon, Eugene, OR 97403, USA.
Institute of Neuroscience, Department of Biology, 1254 University of Oregon, Eugene, OR 97403, USA.
Development. 2018 Feb 23;145(4):dev155317. doi: 10.1242/dev.155317.
Resident microbes promote many aspects of host development, although the mechanisms by which microbiota influence host tissues remain unclear. We showed previously that the microbiota is required for allocation of appropriate numbers of secretory cells in the zebrafish intestinal epithelium. Because Notch signaling is crucial for secretory fate determination, we conducted epistasis experiments to establish whether the microbiota modulates host Notch signaling. We also investigated whether innate immune signaling transduces microbiota cues via the Myd88 adaptor protein. We provide the first evidence that microbiota-induced, Myd88-dependent signaling inhibits host Notch signaling in the intestinal epithelium, thereby promoting secretory cell fate determination. These results connect microbiota activity via innate immune signaling to the Notch pathway, which also plays crucial roles in intestinal homeostasis throughout life and when impaired can result in chronic inflammation and cancer.
常驻微生物促进宿主发育的多个方面，尽管微生物群影响宿主组织的机制仍不清楚。我们之前表明，斑马鱼肠道上皮中分泌细胞数量的适当分配需要微生物群。由于Notch信号对于分泌命运的决定至关重要，我们进行了上位性实验，以确定微生物群是否调节宿主Notch信号。我们还研究了先天免疫信号是否通过Myd88衔接蛋白转导微生物群信号。我们提供了首个证据，即微生物群诱导的、Myd88依赖性信号传导抑制肠道上皮中的宿主Notch信号，从而促进分泌细胞命运的决定。这些结果将通过先天免疫信号传导的微生物群活性与Notch途径联系起来，Notch途径在整个生命过程中的肠道稳态中也起着关键作用，受损时可导致慢性炎症和癌症。
