A conserved Notch-Meis1-Pbx cascade specifies secretory progenitors into spatially diverse intestinal best4 (+) cells.

A conserved Notch-Meis1-Pbx1 cascade directs secretory progenitors to become spatially diverse best4 (+) cells in vertebrate intestines.

• Why it matters: Understanding best4 (+) cell development is crucial because their alteration is linked to inflammatory bowel disease and colorectal cancer, yet their origins and functions are poorly understood, especially in mammals.
• What they did: Using zebrafish as an in vivo model, the study traced best4 (+) cell lineage from secretory progenitors, revealing that Notch/Dll4 signaling induces meis1b expression, which specifies best4 (+) cells, followed by pbx3a-driven regional diversification.
• The result: The findings show best4 (+) cells sense luminal pH and extend projections without restoring pH after challenges, providing insights into their development and a genetic toolkit for future functional studies relevant to intestinal diseases.