Publication: New MCB researcher establishes zebrafish as a model to study recently discovered cell type

best4+ cells are a recently discovered intestinal cell type that becomes altered in diseases like inflammatory bowel disease and colorectal cancer, making their regulation a potential therapeutic target. However, little is known about how these cells develop or function, given their recent discovery and their absence from mice.

To address this, researchers at the NIH used zebrafish, which do have best4+ cells, as a model to study these cells in a living organism. They found that best4+ cells arise from secretory progenitor cells and uncovered the entire developmental gene regulatory network of best4+ cells including key regulators necessary for their identity and spatial diversification. In addition, taking advantage of the optical transparency of zebrafish, researchers genetically modified best4+ cells to report pH changes inside the cell and found that best4+ cells reduced their intracellular pH in response to acidic challenges in the gut lumen indicating that these cells sense pH changes in the gut. 

The Sur Lab is trying to find out what happens after best4+ cells sense pH. 

These findings were published in the journal Genes & Development, with the lead author being Abhinav Sur, who recently joined the MCB Department in May 2026. 

The research details how best4+ cells develop and establishes zebrafish as a genetic model for studying their function, providing a foundation for future research into how these cells might be targeted in disease.

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