Jagged1 and Notch1 help edit M cell patterning in Peyer’s patch follicle epithelium

Mucosal epithelium M cells are dispersed across Peyer’s patch follicle associated epithelium (PPFAE) with minimal clustering. Since Notch signaling can influence patterning in epithelia, we examined its influence on PPFAE M cell distribution. Conditional deletion of Notch1 in intestinal epithelium increased PPFAE M cells and also increased M cell clustering, implying a role for Notch in both M cell numbers and lateral inhibition. By contrast, conditional deletion of the ligand Jagged1 also increased M cell clustering, but with a paradoxical decrease in M cell density. In vitro, inhibition of Notch signaling reduced expression of an M cell associated gene CD137, consistent with cis-promoting effects on M cell development. Thus, Jagged1 may have a cis-promoting role in committed M cells, but a trans-inhibitory effect on neighboring cells. In sum, Jagged1–Notch signaling may edit the pattern of M cells across the PPFAE, which may help optimize mucosal immune surveillance.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (137 K)Download as PowerPoint slideHighlights► Notch and Jagged1 genes were floxed in intestinal epithelium. ► Floxed Notch1 caused a doubling of villous goblet cell numbers. ► Floxed Notch1 increased both Peyer’s patch M cell numbers and clustering. ► Floxed Jagged1 decreased M cell numbers but increased clustering. ► In vitro, M cell genes Jagged1 and CD137 were coordinately induced.