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Activin receptor patterning of foregut organogenesis
Open accessAbstract
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.
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“FGF2 and Activin, secreted by the notochord, lead to the expression of pancreatic markers by repressing expression of Shh in pancreatic endoderm [15-19].”
From A systematic screen for genes expressed in definitive endoderm by Serial Analysis of Gene Expression (SAGE) (2007) · cites this paper as [17]
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Ameri, J. (2010) · Lund University Publications (Lund University) · Cited by 1
Bone Morphogenetic Protein Receptors and Actions
Miyazono, K. (2002) · Elsevier eBooks · doi:10.1016/b978-012098652-1.50153-0 · Cited by 1
Expression and Functional Analysis of Vsig1 Gene
Oidovsambuu, O. (2009) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-337 · Cited by 1
Unger, L., Larsen, U., Legøy, T. A., Hossain, M. K., Gudmestad, J. H., Friestad, A., Sharmine, S., Njølstad, P., Ræder, H., Herrera, P., et al. (2026) · Genes & Development · doi:10.1101/gad.353153.125 · Cited by 2
“…is essential for pancreatic specification during development in vertebrates (Kim and Hebrok 2001; Hebrok 2003) from fish (Roy et al. 2001) to chicks (Hebrok et al. 1998), mice (Apelqvist et al. 1997; Hebrok et al. 2000; Kim et al. 2000; Ramalho-Santos et al. 2000), and humans (Klieser et al. 2016).”
Pancreatic Progenitor Cells in Injury and Regeneration
Afelik, S., & Jensen, J. (2008) · Springer eBooks · doi:10.1007/978-0-387-69252-4_7
Molecular diversity in the Notch receptor family
Beatus, P. (2001) · Figshare
Development and Life Cycle of a β‐Cell
Serup, P., & Nielsen, J. H. (2003) · doi:10.1002/0470862092.d0201 · Cited by 1
Role of BMP signaling and ASNA1 in β-cells
Goulley, J. (2008) · DiVA at Umeå University (Umeå University)
Hair growth control by follistatin
Nakamura, M., & Miyachi, Y. (2004) · Inflammation and Regeneration · doi:10.2492/jsir.24.573
Activin a in Fetuses of Non-Diabetic and Streptozotocin-induced Diabetic Mother Rats.
Kohama, T., Abe, Y., & Kobayashi, I. (2003) · The Kitakanto Medical Journal · doi:10.2974/kmj.53.21
Expression and regulation of human activins and their receptors
Hildén, K. (2002) · Työväentutkimus Vuosikirja
Hedgehog signaling in pancreas development and the regulation of insulin production
Thomas, M. K. (2002) · Current Opinion in Endocrinology & Diabetes · doi:10.1097/00060793-200204000-00007
Development and Regulatory Signaling in the Pancreas
Korc, M. (2003) · Elsevier eBooks · doi:10.1016/b978-012124546-7/50700-2
Metadata
- Authors
- Kim, S. K., Hebrok, M., Li, E., Oh, S. P., Schrewe, H., Harmon, E. B., Lee, J. S., & Melton, D. A.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2000-08-01
- Volume
- 14
- Issue
- 15
- Pages
- 1866-1871
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC316826
- OpenAlex
- W1768073869
- Cited by
- 212
- References
- 33
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2021: 1 · 2020: 6 · 2019: 3 · 2018: 9 · 2017: 5 · 2016: 5 · 2015: 8 · 2014: 8 · 2013: 8 · 2012: 10
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- American Diabetes Association
- Donald E. and Delia B. Baxter Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- activin receptors, ActRIIA, ActRIIB, pancreatic islets, endocrine pancreas, hypoinsulinemia, glucose tolerance, stomach development, spleen development, Sonic hedgehog, Isl1, axial patterning, mouse mutants
- MeSH terms
- Animals, Cell Differentiation, Digestive System, Digestive System Physiological Phenomena, Glucose Tolerance Test, Hyperplasia, Insulin, Male, Mice, Mutant Strains, Nerve Tissue Proteins, Pancreas, Proteins, Spleen, Stomach, Transcription Factors, Trans-Activators, Receptors, Growth Factor, Homeodomain Proteins, Body Patterning, Activin Receptors, Type II, Mice, Hedgehog Proteins, LIM-Homeodomain Proteins
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