Notochord repression of endodermal Sonic hedgehog permits pancreas development
Open accessAbstract
Notochord signals to the endoderm are required for development of the chick dorsal pancreas. Sonic hedgehog (SHH) is normally absent from pancreatic endoderm, and we provide evidence that notochord, in contrast to its effects on adjacent neuroectoderm where SHH expression is induced, represses SHH expression in adjacent nascent pancreatic endoderm. We identify activin-βB and FGF2 as notochord factors that can repress endodermal SHH and thereby permit expression of pancreas genes including Pdx1 and insulin. Endoderm treatment with antibodies that block hedgehog activity also results in pancreatic gene expression. Prevention of SHH expression in prepancreatic dorsal endoderm by intercellular signals, like activin and FGF, may be critical for permitting early steps of chick pancreatic development.
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FGF2 and Activin, secreted by the notochord, lead to expression of pancreatic markers by repressing Shh in pancreatic endoderm.
“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 [15]
The “Notochord factors activin and FGF initiate pancreatic differentiation” section reports that activin-βB reduces endodermal Shh and induces the pancreatic markers Pdx1 and insulin. Figure 4 reports notochord expression of activin-βB and FGF2, but the “possible role” section says FGF2’s effects are concentration-dependent and that further work is needed to determine whether it is an endogenous notochord signal. Thus the paper does not establish that notochord-secreted FGF2 drives pancreatic-marker expression in the way the sentence states. (LLM, conf=0.88)
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Cites
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Notochord to endoderm signaling is required for pancreas development
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Stromal response to Hedgehog signaling restrains pancreatic cancer progression
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Anterior definitive endoderm from ESCs reveals a role for FGF signaling
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Epithelial and stromal co-evolution and complicity in pancreatic cancer
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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].”
BackgroundLoss of TBX3 enhances pancreatic progenitor generation from human pluripotent stem cells
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- Authors
- Hebrok, M., Kim, S. K., & Melton, D. A.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1998-06-01
- Volume
- 12
- Issue
- 11
- Pages
- 1705-1713
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC316875
- OpenAlex
- W2142986021
- Cited by
- 628
- References
- 2
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 9 · 2023: 14 · 2022: 16 · 2021: 16 · 2020: 18 · 2019: 13 · 2018: 14 · 2017: 17 · 2016: 19 · 2015: 24 · 2014: 19 · 2013: 16 · 2012: 20
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- notochord, Sonic hedgehog, pancreatic development, dorsal pancreas, FGF2, PDX1, insulin, Hedgehog signaling, chick embryo, endoderm patterning
- MeSH terms
- Animals, Chick Embryo, Embryonic Induction, Oligopeptides, Pancreas, Peptides, Proteins, Trans-Activators, Gene Expression Regulation, Developmental, Activins, Hedgehog Proteins
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