Development of distinct intestinal epithelial cell types is central to normal gut function, and is aberrant in diseases such as cancer. Gene targeting experiments performed in our laboratory revealed that the mouse atonal homolog 1 (Math1) is essential for the formation of most intestinal secretory lineages and suggested an early fate decision between the absorptive and secretory lineages is mediated by Math1. I plan to determine the effects of Math1 loss in the adult intestine, as well as how the secretory lineage defects arise. I hypothesize that (1) Math1 is expressed in a single precursor that is competent to produce all secretory but not absorptive lineages; (2) normal secretory function is necessary for development and proliferative homeostasis of the intestine. I will address these aims by determining Math1 's role in the generation and proliferation of the epithelium of the postnatal intestine, using the Cre/loxP recombination system to specifically delete Math1 in the intestine. I also propose to fate-map Math1 expressing cells to define the ontogenic hierarchy of epithelial cells in normal and Math1-null intestine. These experiments will allow us to elucidate molecular steps required for genesis of the secretory lineages of the intestine, and provide insight into the regulation of development and proliferation in the intestinal mucosa.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DK063747-01
Application #
6584380
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Podskalny, Judith M,
Project Start
2003-05-01
Project End
2005-04-30
Budget Start
2003-05-01
Budget End
2004-04-30
Support Year
1
Fiscal Year
2003
Total Cost
$46,420
Indirect Cost
Name
Baylor College of Medicine
Department
Genetics
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Shroyer, Noah F; Helmrath, Michael A; Wang, Vincent Y-C et al. (2007) Intestine-specific ablation of mouse atonal homolog 1 (Math1) reveals a role in cellular homeostasis. Gastroenterology 132:2478-88
Shroyer, Noah F; Wallis, Deeann; Venken, Koen J T et al. (2005) Gfi1 functions downstream of Math1 to control intestinal secretory cell subtype allocation and differentiation. Genes Dev 19:2412-7