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Control of endodermal endocrine development by Hes-1
J Jensen1, E E Pedersen, P Galante
1Department of Developmental Biology, Hagedorn Research Institute, Denmark.
Nature Genetics
|December 30, 1999
Summary
Hes-1 deficiency in mice leads to pancreatic hypoplasia and accelerated endocrine cell differentiation. This study reveals Hes-1 as a key negative regulator of endodermal endocrine development in the stomach and gut.
Area of Science:
- Developmental biology
- Endocrinology
- Molecular genetics
Background:
- Endoderm development involves basic helix-loop-helix (bHLH) proteins, which regulate neuronal and endocrine cell differentiation.
- The Notch pathway and Hairy and Enhancer-of-split (HES)-type proteins antagonize bHLH factors during differentiation.
Purpose of the Study:
- To investigate the role of Hes-1 in endodermal endocrine cell development.
- To determine the impact of Hes-1 deficiency on pancreatic and gastrointestinal endocrine cell formation.
Main Methods:
- Analysis of Hes1-deficient mice.
- Assessment of pancreatic hypoplasia and endocrine cell differentiation.
- Evaluation of bHLH component expression in the developing stomach and gut.
Main Results:
- Hes1-deficient mice exhibit severe pancreatic hypoplasia.
- Accelerated differentiation of post-mitotic glucagon-expressing endocrine cells was observed.
- Upregulation of bHLH factors correlated with precocious and excessive differentiation of multiple endocrine cell types in the stomach and gut.
Conclusions:
- Hes-1 acts as a general negative regulator of endodermal endocrine differentiation.
- Loss of Hes-1 function results in premature and excessive endocrine cell development.
- Hes-1 is crucial for controlling the timing and extent of endocrine cell formation in the developing endoderm.