The overall goal of the research is to better understand the mechanisms underlying the full differentiation of the developing pancreas with all of its components (endocrine, exocrine, and mesenchymal). One of the key steps in the regulation of pancreatic development is the induction of precursor or stem cells to form the insulin-producing beta cells of the islets of Langerhans. The investigators research has focused on tissue interaction studies in the developing mouse pancreas. The investigators, and others, have found that the embryonic pancreatic mesenchyme is a critical regulator of endocrine versus exocrine pancreatic lineage-selection by the developing pancreatic epithelium. In addition, however, the investigators have found that the mesenchyme undergoes maturation in its inductive capacity. With development, the mesenchyme seems to acquire an enhanced ability to induce more mature exocrine structures, while at the same time it becomes able to induce a greater number of insulin-positive endocrine cells. Interestingly, these insulin-positive cells are only those cells noti in contact with the mesenchyme, whereas the exocrine cells appear to all be in contact with mesenchyme. Thus, the investigators hypothesize that there is/are diffusible factor(s) in the mesenchyme that control endocrine pancreatic differentiation, and beta cell differentiation in particular. These factors may be beta cell inhibitors, present in immature mesenchyme, which disappear with age, or else beta cell inducers, which appear in later-aged mesenchyme. The purpose of this proposal is to use differential analyses of gene expression to compare young versus old pancreatic mesenchyme. In this way the investigators hope to find, for the first time, endogenous inducer(s) of beta cell differentiation. Such an inducer would have obvious potential for clinical therapy.
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| Li, Zhixing; Manna, Pradip; Kobayashi, Hiroyuki et al. (2004) Multifaceted pancreatic mesenchymal control of epithelial lineage selection. Dev Biol 269:252-63 |
| Kobayashi, Hiroyuki; Spilde, Troy L; Li, Zhixing et al. (2002) Lectin as a marker for staining and purification of embryonic pancreatic epithelium. Biochem Biophys Res Commun 293:691-7 |
| Prasadan, Krishna; Daume, Erica; Preuett, Barry et al. (2002) Glucagon is required for early insulin-positive differentiation in the developing mouse pancreas. Diabetes 51:3229-36 |
| Kobayashi, Hiroyuki; Spilde, Troy L; Bhatia, Amina M et al. (2002) Retinoid signaling controls mouse pancreatic exocrine lineage selection through epithelial-mesenchymal interactions. Gastroenterology 123:1331-40 |
