Seminar Title: "New Cell on the Block: Decoding the origins and potential of the newly discovered intestinal best4+ cells"
When
Sept. 22, 2026, 3:30 – 4:45 p.m.
Where
Haury, Room 216
Presenter Details
Seminar Information
best4+ cells are a recently described vertebrate intestinal epithelial cell type. best4+ cells are altered in inflammatory bowel disease and colorectal cancer, suggesting that stimulation of their homeostatic replenishment may have therapeutic potential. However, the development and function of best4+ cells remain unclear. Since mice lack best4+ cells, we established zebrafish as a tractable in vivo model to observe, manipulate, and remove best4+ cells in an organismal context. We dissected best4+ cell developmental regulation in vivo from birth to differentiation and specialization, focusing on factors conserved in best4+ cells across vertebrates. Lineage tracing demonstrated that best4+ cells arise from secretory progenitors, where Notch/Dll4 signaling mediates a decision between best4+ and enterochromaffin cells by triggering meis1b expression. Following specification by meis1b, pbx3a spatially diversifies best4+ cells, which develop regional heterogeneity in gene expression, intracellular pH, and function. In vivo live imaging and removal of best4+ cells showed that best4+ cells sense luminal pH changes and extend dynamic luminal and stromal projections, but are not required to restore global luminal pH after challenge. Altogether, this study experimentally delineates best4+ cell developmental regulation and develops a genetic toolkit to examine their function in vivo, both of which will aid investigating how best4+ cells are altered or can be restored during disease.
Seminar Host
Dr. Lisa Nagy, MCB
Contacts
Whitney DeGroot