Highlights d Zebrafish possess genetically distinct IEC populations d Zebrafish have IECs analogous to mammalian progenitor, Best4/Otop2, and tuft cells d Microbes alter unique transcriptional pathways within intestinal cell subtypes d Microbes promote intestinal angiogenesis

No abstract

The intestinal epithelium contains secretory and absorptive cell lineages that develop from undifferentiated progenitor cells. Despite the collective importance of these cells to host responses against microbial invaders, little is known about the contributions of immune responses in individual cell types to the maintenance of intestinal homeostasis. In this study, we asked how inhibition of immune pathway activity exclusively in progenitor cells, or in differentiated enterocytes, affects midgut homeostasis in adult Drosophila. We found that blocking immune activity in enterocytes rendered flies more tolerant of Vibrio cholerae infection, had negligible effects on the gut bacterial microbiome, and significantly affected metabolism. In contrast, inhibition of immune activity in progenitors rendered flies less tolerant of Vibrio infections, modified host association with Lactobacillus symbionts, and blocked growth and renewal in the midgut epithelium. Together, these data uncover substantial cell type-specific contributions of epithelial immunity to adult intestinal homeostasis.

Highlights d Loss of Myt1 promotes intestinal stem cell proliferation d Myt1 activity promotes both mitotic cell cycle exit and differentiation of enteroblasts d Myt1 inhibition of cyclin A/Cdk1 prevents enteroblast mitosis

The intestinal epithelium is a complex tissue monolayer composed of regionally and functionally specialized intestinal epithelial cells. Given epithelial exposure to harsh and varied luminal conditions, epithelial cells continuously regenerate to sustain the barrier against environmental factors, including microbial invaders. Multipotent intestinal stem cells are essential to epithelial regenerative capacity, generating a programed mixture of absorptive and secretory cell types. Mechanisms of epithelial growth and differentiation in response to endogenous or external stressors remain under investigation. In this review, we highlight the zebrafish, Danio rerio, as a potent model of intestinal epithelial development and function. We describe epithelial composition and key regulators of epithelial renewal to promote the zebrafish as an investigative tool to study epithelial development and growth. We also highlight areas for discovery, particularly in the context of stress-dependent regulation of epithelial function.