Division of Gastroenterology, Department of Medicine
Amino Acids, Peptides, and Proteins | Cell Biology | Developmental Biology | Digestive System | Endocrine System | Gastroenterology | Hormones, Hormone Substitutes, and Hormone Antagonists | Nutritional and Metabolic Diseases
Transcription factor Neurod1 is required for enteroendocrine progenitor differentiation and maturation. Several earlier studies indicated that ectopic expression of Neurod1 converted non- neuronal cells into neurons. However, the functional consequence of ectopic Neurod1 expression has not been examined in the GI tract, and it is not known whether Neurod1 can similarly switch cell fates in the intestine. We generated a mouse line that would enable us to conditionally express Neurod1 in intestinal epithelial cells at different stages of differentiation. Forced expression of Neurod1 throughout intestinal epithelium increased the number of EECs as well as the expression of EE specific transcription factors and hormones. Furthermore, we observed a substantial reduction of Paneth cell marker expression, although the expressions of enterocyte-, tuft- and goblet-cell specific markers are largely not affected. Our earlier study indicated that Neurog3+ progenitor cells give rise to not only EECs but also Goblet and Paneth cells. Here we show that the conditional expression of Neurod1 restricts Neurog3+ progenitors to adopt Paneth cell fate, and promotes more pronounced EE cell differentiation, while such effects are not seen in more differentiated Neurod1+ cells. Together, our data suggest that forced expression of Neurod1 programs intestinal epithelial cells more towards an EE cell fate at the expense of the Paneth cell lineage and the effect ceases as cells mature to EE cells.
Differentiation, Endocrine system and metabolic diseases
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DOI of Published Version
Sci Rep. 2019 Dec 20;9(1):19489. doi: 10.1038/s41598-019-55292-7. Link to article on publisher's site
Li JH, Ray S, Pan N, Haigh J, Fritzsch B, Leiter AB. (2019). Intestinal Neurod1 expression impairs paneth cell differentiation and promotes enteroendocrine lineage specification. Open Access Articles. https://doi.org/10.1038/s41598-019-55292-7. Retrieved from https://escholarship.umassmed.edu/oapubs/4106
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This work is licensed under a Creative Commons Attribution 4.0 License.
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