Control of endodermal endocrine development by Hes-1.
Development of endocrine cells in the endoderm involves Atonal and Achaete/Scute-related basic helix-loop-helix (bHLH) proteins. These proteins also serve as neuronal determination and differentiation factors, and are antagonized by the Notch pathway partly acting through Hairy and Enhancer-of-split (HES)-type proteins. Here we show that mice deficient in Hes1 (encoding Hes-1) display severe pancreatic hypoplasia caused by depletion of pancreatic epithelial precursors due to accelerated differentiation of post-mitotic endocrine cells expressing glucagon. Moreover, upregulation of several bHLH components is associated with precocious and excessive differentiation of multiple endocrine cell types in the developing stomach and gut, showing that Hes-1 operates as a general negative regulator of endodermal endocrine differentiation.
Jensen
J
J
Department of Developmental Biology, Hagedorn Research Institute, Denmark.
Pedersen
E E
EE
Galante
P
P
Hald
J
J
Heller
R S
RS
Ishibashi
M
M
Kageyama
R
R
Guillemot
F
F
Serup
P
P
Madsen
O D
OD
D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins; D004702:Endocrine Glands / Q000166:cytology / Q000196:embryology*; D004707:Endoderm; D018507:Gene Expression Regulation, Developmental; D018257:Helix-Loop-Helix Motifs; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D019476:Insect Proteins / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010179:Pancreas / Q000196:embryology / Q000473:pathology / Q000503:physiopathology; D011506:Proteins / Q000378:metabolism; D051880:Receptors, Notch; D012097:Repressor Proteins; D015398:Signal Transduction; D013270:Stomach / Q000473:pathology; D000072056:Transcription Factor HES-1
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; D011506:Proteins; D051880:Receptors, Notch; D012097:Repressor Proteins; D000072056:Transcription Factor HES-1; C084530:E(spl)mdelta-HLH protein, Drosophila; C489734:Hes1 protein, mouse