Activin receptor patterning of foregut organogenesis.
Foregut development produces a characteristic sequence of gastrointestinal and respiratory organs, but the signaling pathways that ensure this developmental order remain largely unknown. Here, mutations of activin receptors ActRIIA and ActRIIB are shown to disrupt the development of posterior foregut-derived organs, including the stomach, pancreas, and spleen. Foregut expression of genes including Shh and Isl1 is shifted in mutant mice. The endocrine pancreas is particularly sensitive to the type and extent of receptor inactivation. ActRIIA(+/-)B(+/-) animals lack axial defects, but have hypoplastic pancreatic islets, hypoinsulinemia, and impaired glucose tolerance. Thus, activin receptor-mediated signaling regulates axial patterning, cell differentiation, and function of foregut-derived organs.
Department of Developmental Biology, Stanford University, Stanford, California 94305-5329 USA. seungkim@cmgm.stanford.edu
S K
SK
Kim
M
M
Hebrok
E
E
Li
S P
SP
Oh
H
H
Schrewe
E B
EB
Harmon
J S
JS
Lee
D A
DA
Melton
D030301:Activin Receptors, Type II; D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D002454:Cell Differentiation; D004064:Digestive System / Q000196:embryology; D004068:Digestive System Physiological Phenomena; D005951:Glucose Tolerance Test; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006965:Hyperplasia; D007328:Insulin / Q000097:blood; D060850:LIM-Homeodomain Proteins; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins; D010179:Pancreas / Q000196:embryology* / Q000473:pathology / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000002:abnormalities / Q000502:physiology; D013270:Stomach / Q000002:abnormalities / Q000196:embryology; D015534:Trans-Activators; D014157:Transcription Factors
D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D007328:Insulin; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D017978:Receptors, Growth Factor; D015534:Trans-Activators; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; D030301:Activin Receptors, Type II