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Genetic identification of a novel NeuroD1 function in the early differentiation of islet alpha, PP and epsilon cells.

ABSTRACT: 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.

SUBMITTER: Chao CS

PROVIDER: S-EPMC2174610 | biostudies-literature | 2007 Dec

REPOSITORIES: biostudies-literature

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Genetic identification of a novel NeuroD1 function in the early differentiation of islet alpha, PP and epsilon cells.

Chao Christina S CS Loomis Zoe L ZL Lee Jacqueline E JE Sussel Lori L

Developmental biology 20071005 2

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 ...[more]

PMID: 17988662

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Dataset Information

Genetic identification of a novel NeuroD1 function in the early differentiation of islet alpha, PP and epsilon cells.

Publications

Genetic identification of a novel NeuroD1 function in the early differentiation of islet alpha, PP and epsilon cells.

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