|Start Date / Time||February 12, 2014 at 9:00 AM|
|End Date / Time||February 12, 2014 at 9:55 AM|
|Location||512 Light Hall|
|Presenter Name||Stefanie Gross (Lori Sussel's lab, Columbia Univer|
|Presentation Title||Nkx2.2: A major regulator of the intestinal epithelium|
|Status||This meeting has already occurred|
The intestine is an excellent tissue to study stem cells and how they are regulated. The stem cells reside in the crypt region, whereas most differentiated cells (enteroendocrine, goblet and tuft cells, enterocytes) are found in the villus compartment. The homeodomain transcription factor Nkx2.2 is expressed in enteroendocrine cells in the villus as well as in the crypt compartment. In the small intestine, Nkx2.2 is first detected at E15.5, and its expression is maintained throughout adulthood. Nkx2.2 is known to regulate cell fate decisions in the enteroendocrine cell lineages of the embryonic intestinal epithelium. Lineage tracing of Nkx2.2 in the adult intestine with a constitutive Nkx2.2:Cre knockin and a Rosa26-Tomato reporter revealed that Nkx2.2 is not only giving rise to the enteroendocrine cell lineage, but to all other cell types in the intestinal epithelium. Several completely Tomato+ crypt/villus units can be detected as well as single Tomato+ goblet, Paneth and enteroendocrine cells. To analyze if Nkx2.2 is expressed in a stem cell population, heterozygous Nkx2.2:LacZ knockin mice were crossed to Lgr5-EGFP-IRES-CreERT2 or Bmi1-EGFP mice identifying Nkx2.2+ cells coexpressing Lgr5-GFP or Bmi1-EGFP. However, radiation injury of adult heterozygous Nkx2.2:LacZ mice with a 12 Gy lethal dose revealed that Nkx2.2 expressing cells are radiation resistant. Analysis of an intestine specific deletion of Nkx2.2 indicates that Nkx2.2 is necessary to maintain proper stem cell numbers and/or is involved in regulating stem cell proliferation, since these mice have an elongated intestine. Further analysis is underway to clarify the role of Nkx2.2 in the adult intestine.