ArticlePloS one2015
Definition of critical periods for Hedgehog pathway antagonist-induced holoprosencephaly, cleft lip, and cleft palate.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 67 citations in OpenAlex.
- Effects of Smoothened Agonist Exposure on Murine Craniofacial Development.International dental journal · 2026Article
- A cell-based Sonic Hedgehog signaling transduction system to identify additive and synergistic chemical interactions.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Advanced Strategies in the Repair of Alveolar Cleft Defects: Biological Approaches, Biomaterials, and Future Perspectives.Progress in molecular and subcellular biology · 2026Review
- The Role of the Hedgehog Pathway in Alcohol-Induced Birth Defects.Advances in experimental medicine and biology · 2026Review
- Cranial base synostosis in mice caused by upregulation of Wnt following partial inhibition of Shh.BMC biology · 2025Article
- Examining the Neurodevelopmental Impact of Sonic Hedgehog Pathway Inhibition in Mice.Birth defects research · 2025Article
- On the Maxillofacial Development of Mice, Mus musculus.Journal of morphology · 2025Article
- Examination of piperonyl butoxide developmental toxicity as a Sonic hedgehog pathway inhibitor targeting limb and palate morphogenesis.Reproductive toxicology (Elmsford, N.Y.) · 2024Article
- Efcab7 deletion sensitizes mice to the teratogenic effects of gastrulation-stage alcohol exposure.Reproductive toxicology (Elmsford, N.Y.) · 2024Article
- Pharmacokinetic analysis of acute and dietary exposure to piperonyl butoxide in the mouse.Toxicology reports · 2023Article
- Review
- Frem1 activity is regulated by Sonic hedgehog signaling in the cranial neural crest mesenchyme during midfacial morphogenesis.Developmental dynamics : an official publication of the American Association of Anatomists · 2023Article
- Gene-environment interactions in birth defect etiology: Challenges and opportunities.Current topics in developmental biology · 2023Review
- Pharmacological activation of the Sonic hedgehog pathway with a Smoothened small molecule agonist ameliorates the severity of alcohol-induced morphological and behavioral birth defects in a zebrafish model of fetal alcohol spectrum disorder.Journal of neuroscience research · 2022Article
- Engineering Epithelial-Mesenchymal Microtissues to Study Cell-Cell Interactions in Development.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Δ9-Tetrahydrocannabinol inhibits Hedgehog-dependent patterning during development.Development (Cambridge, England) · 2021Article
- Gene-teratogen interactions influence the penetrance of birth defects by altering Hedgehog signaling strength.Development (Cambridge, England) · 2021Article
- Examining the developmental toxicity of piperonyl butoxide as a Sonic hedgehog pathway inhibitor.Chemosphere · 2021Review
- Developmental malformations resulting from high-dose maternal tamoxifen exposure in the mouse.PloS one · 2021Article
- A Microphysiological Approach to Evaluate Effectors of Intercellular Hedgehog Signaling in Development.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The Hedgehog (Hh) signaling pathway mediates multiple spatiotemporally-specific aspects of brain and face development. Genetic and chemical disruptions of the pathway are known to result in an array of structural malformations, including holoprosencephaly (HPE), clefts of the lip with or without cleft palate (CL/P), and clefts of the secondary palate only (CPO). Here, we examined patterns of dysmorphology caused by acute, stage-specific Hh signaling inhibition. Timed-pregnant wildtype C57BL/6J mice were administered a single dose of the potent pathway antagonist vismodegib at discrete time points between gestational day (GD) 7.0 and 10.0, an interval approximately corresponding to the 15th to 24th days of human gestation. The resultant pattern of facial and brain dysmorphology was dependent upon stage of exposure. Insult between GD7.0 and GD8.25 resulted in HPE, with peak incidence following exposure at GD7.5. Unilateral clefts of the lip extending into the primary palate were also observed, with peak incidence following exposure at GD8.875. Insult between GD9.0 and GD10.0 resulted in CPO and forelimb abnormalities. We have previously demonstrated that Hh antagonist-induced cleft lip results from deficiency of the medial nasal process and show here that CPO is associated with reduced growth of the maxillary-derived palatal shelves. By defining the critical periods for the induction of HPE, CL/P, and CPO with fine temporal resolution, these results provide a mechanism by which Hh pathway disruption can result in "non-syndromic" orofacial clefting, or HPE with or without co-occurring clefts. This study also establishes a novel and tractable mouse model of human craniofacial malformations using a single dose of a commercially available and pathway-specific drug.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.