Cited by 860Hedgehog Signaling Pathway StudiesPharmacological Effects and Toxicity StudiesGenetic and Kidney Cyst Diseases

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Teratogen-Mediated Inhibition of Target Tissue Response to Shh Signaling

Cooper, Michael K., Porter, Jeffery A., Young, Keith E., Beachy, Philip A.·1998·Science

DOI 10.1126/science.280.5369.1603

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Abstract

Veratrum alkaloids and distal inhibitors of cholesterol biosynthesis have been studied for more than 30 years as potent teratogens capable of inducing cyclopia and other birth defects. Here, it is shown that these compounds specifically block the Sonic hedgehog (Shh) signaling pathway. These teratogens did not prevent the sterol modification of Shh during autoprocessing but rather inhibited the response of target tissues to Shh, possibly acting through the sterol sensing domain within the Patched protein regulator of Shh response.

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Authors: Cooper, M. K., Porter, J. A., Young, K. E., & Beachy, P. A.
Affiliations: Howard Hughes Medical Institute (US)
Corresponding author: Porter, Jeffery A.
Beachy, Philip A.
ORCID: Beachy, Philip A.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1998-06-05
Volume: 280
Issue: 5369
Pages: 1603-1607
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.280.5369.1603
OpenAlex: W2002249795
Cited by: 848
References: 26
Citations by year: 2026: 7 · 2025: 7 · 2024: 12 · 2023: 13 · 2022: 18 · 2021: 9 · 2020: 16 · 2019: 25 · 2018: 22 · 2017: 25 · 2016: 26 · 2015: 27 · 2014: 34 · 2013: 31 · 2012: 50
FWCI: 14.39
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
Keywords: teratogens, Sonic hedgehog signaling, veratrum alkaloids, cholesterol biosynthesis inhibitors, cyclopia, congenital malformations, sterol-sensing domain
MeSH terms: Abnormalities, Drug-Induced, Patched Receptors, Animals, trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride, Cell Membrane, Central Nervous System, Chick Embryo, Cholesterol, DNA-Binding Proteins, Endoplasmic Reticulum, Membrane Proteins, Muscle Proteins, Nerve Tissue Proteins, Nuclear Proteins, Proteins, Receptors, Cell Surface, Teratogens, Tomatine, Transcription Factors, Triparanol, Veratrum Alkaloids, Signal Transduction, Trans-Activators, Holoprosencephaly, Homeodomain Proteins, Culture Techniques, Hepatocyte Nuclear Factor 3-beta, PAX7 Transcription Factor, Hedgehog Proteins, LIM-Homeodomain Proteins

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Teratogen-Mediated Inhibition of Target Tissue Response to Shh Signaling

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