Hnf6-dependent synthesis of Ngn3 protein during morphogenesis

Stable Identifier
R-MMU-186583
Type
Reaction [omitted]
Species
Mus musculus
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5/5
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Hnf6-dependent synthesis of Ngn3 protein during morphogenesis
The Ngn3 gene is transcribed, its mRNA is translated, and the protein product is transported to the nucleus during morphogenesis of the pancreas. Ngn3 transcription requires the activity of the Hnf6 transcription factor - in vivo, expression of Ngn3 was almost abolished in murine Hnf6 -/- embryos (Jacquemin et al. 2000). Hes1 represses Ngn3 transcription. Hes1 is an effector of the Notch pathway, which in turn negatively regulates pancreatic development. Lack of Delta-like gene 1 (Notch receptor) or RBP-Jkappa (Notch signaling intracellular mediator) leads to precocious pancreatic endocrine differentiation. Inactivation of Notch/Hes1 is critical for endocrine (and progenitor/exocrine) pancreatic differentiation (Apelqvist et al. 1999; Jensen et al. 2000). In vivo, the interplay between Hnf6 and Hes1 deteremines the timing and level of Ngn3 expression, which is critical for normal development of the pancreas.
Literature References
PubMed ID Title Journal Year
10615124 Control of endodermal endocrine development by Hes-1

Serup, P, Hald, J, Madsen, OD, Pedersen, EE, Ishibashi, M, Heller, RS, Guillemot, F, Galante, P, Jensen, J, Kageyama, R

Nat Genet 2000
10825208 Transcription factor hepatocyte nuclear factor 6 regulates pancreatic endocrine cell differentiation and controls expression of the proendocrine gene ngn3

Rousseau, GG, Collen, D, Madsen, OD, Dewerchin, M, Jacquemin, P, Lemaigre, FP, Godfraind, C, Gradwohl, G, Carmeliet, P, Guillemot, F, Jensen, J, Durviaux, SM

Mol Cell Biol 2000
10476967 Notch signalling controls pancreatic cell differentiation

Honjo, T, Beatus, P, Anderson, DJ, Li, H, Apelqvist, A, Sommer, L, Edlund, H, Hrabe de Angelis, M, Lendahl, U

Nature 1999
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