| First Author | Chao CS | Year | 2007 |
| Journal | Dev Biol | Volume | 312 |
| Issue | 2 | Pages | 523-32 |
| PubMed ID | 17988662 | Mgi Jnum | J:129103 |
| Mgi Id | MGI:3768695 | Doi | 10.1016/j.ydbio.2007.09.057 |
| Citation | Chao CS, et al. (2007) Genetic identification of a novel NeuroD1 function in the early differentiation of islet alpha, PP and epsilon cells. Dev Biol 312(2):523-32 |
| abstractText | Nkx2.2 and NeuroD1 are vital for proper differentiation of pancreatic islet cell types. Nkx2.2-null mice fail to form beta cells, have reduced numbers of alpha and PP cells and display an increase in ghrelin-producing epsilon cells. NeuroD1-null mice display a reduction of alpha and beta cells after embryonic day (e) 17.5. To begin to determine the relative contributions of Nkx2.2 and NeuroD1 in islet development, we generated Nkx2.2-/-;NeuroD1-/- double knockout (DKO) mice. As expected, the DKO mice fail to form beta cells, similar to the Nkx2.2-null mice, suggesting that the Nkx2.2 phenotype may be dominant over the NeuroD1 phenotype in the beta cells. Surprisingly, however, the alpha, PP and epsilon phenotypes of the Nkx2.2-null mice are partially rescued by the simultaneous elimination of NeuroD1, even at early developmental time points when NeuroD1 null mice alone do not display a phenotype. Our results indicate that Nkx2.2 and NeuroD1 interact to regulate pancreatic islet cell fates, and this epistatic relationship is cell-type dependent. Furthermore, this study reveals a previously unappreciated early function of NeuroD1 in regulating the specification of alpha, PP and epsilon cells. |
