| First Author | Brischetto C | Year | 2021 |
| Journal | Development | Volume | 148 |
| Issue | 21 | PubMed ID | 34751748 |
| Mgi Jnum | J:330254 | Mgi Id | MGI:6814643 |
| Doi | 10.1242/dev.199683 | Citation | Brischetto C, et al. (2021) NF-kappaB determines Paneth versus goblet cell fate decision in the small intestine. Development 148(21):dev199683 |
| abstractText | Although the role of the transcription factor NF-kappaB in intestinal inflammation and tumor formation has been investigated extensively, a physiological function of NF-kappaB in sustaining intestinal epithelial homeostasis beyond inflammation has not been demonstrated. Using NF-kappaB reporter mice, we detected strong NF-kappaB activity in Paneth cells, in '+4/+5' secretory progenitors and in scattered Lgr5+ crypt base columnar stem cells of small intestinal (SI) crypts. To examine NF-kappaB functions in SI epithelial self-renewal, mice or SI crypt organoids ('mini-guts') with ubiquitously suppressed NF-kappaB activity were used. We show that NF-kappaB activity is dispensable for maintaining SI epithelial proliferation, but is essential for ex vivo organoid growth. Furthermore, we demonstrate a dramatic reduction of Paneth cells in the absence of NF-kappaB activity, concomitant with a significant increase in goblet cells and immature intermediate cells. This indicates that NF-kappaB is required for proper Paneth versus goblet cell differentiation and for SI epithelial homeostasis, which occurs via regulation of Wnt signaling and Sox9 expression downstream of NF-kappaB. The current study thus presents evidence for an important role for NF-kappaB in intestinal epithelial self-renewal. |
