ArticleDevelopmental biology2014
Direct functional consequences of ZRS enhancer mutation combine with secondary long range SHH signalling effects to cause preaxial polydactyly.
Article in Developmental biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Leveraging genome-wide association analyses with chip and imputed data emerges potential pleiotropic region for four duck growth traits.Scientific reports · 2025Article
- Mirk/Dyrk1B controls ventral spinal cord development via Shh pathway.Cellular and molecular life sciences : CMLS · 2024Article
- ZPA Regulatory Sequence Variants in Chinese Patients With Preaxial Polydactyly: Genetic and Clinical Characteristics.Frontiers in pediatrics · 2022Article
- Preaxial Polydactyly in an Elderly Woman.Case reports in orthopedics · 2022Article
- Case Report: Prenatal Diagnosis of Postaxial Polydactyly With Bi-Allelic Variants in Smoothened (SMO).Frontiers in genetics · 2022Article
- Molecular signatures of selection on the human GLI3 associated central nervous system specific enhancers.Development genes and evolution · 2021Article
- Sylvian fissure development is linked to differential genetic expression in the pre-folded brain.Scientific reports · 2020Article
- Article
- Postaxial limb hypoplasia (PALH): the classification, clinical features, and related developmental biology.Annals of the New York Academy of Sciences · 2017Review
- Two Types of Etiological Mutation in the Limb-Specific Enhancer ofG3 (Bethesda, Md.) · 2017Article
- Preaxial polydactyly following early gestational exposure to the smoothened agonist, SAG, in C57BL/6J mice.Birth defects research · 2017Article
- Article
- Regulation of Hedgehog Signalling Inside and Outside the Cell.Journal of developmental biology · 2016Article
- Article
- Novel KIF7 Mutation in a Tunisian Boy with Acrocallosal Syndrome: Case Report and Review of the Literature.Molecular syndromology · 2015Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Sonic hedgehog (SHH) plays a central role in patterning numerous embryonic tissues including, classically, the developing limb bud where it controls digit number and identity. This study utilises the polydactylous Silkie (Slk) chicken breed, which carries a mutation in the long range limb-specific regulatory element of SHH, the ZRS. Using allele specific SHH expression analysis combined with quantitative protein analysis, we measure allele specific changes in SHH mRNA and concentration of SHH protein over time. This confirms that the Slk ZRS enhancer mutation causes increased SHH expression in the posterior leg mesenchyme. Secondary consequences of this increased SHH signalling include increased FGF pathway signalling and growth as predicted by the SHH/GREM1/FGF feedback loop and the Growth/Morphogen models. Manipulation of Hedgehog, FGF signalling and growth demonstrate that anterior-ectopic expression of SHH and induction of preaxial polydactyly is induced secondary to increased SHH signalling and Hedgehog-dependent growth directed from the posterior limb. We predict that increased long range SHH signalling acts in combination with changes in activation of SHH transcription from the Slk ZRS allele. Through analysis of the temporal dynamics of anterior SHH induction we predict a gene regulatory network which may contribute to activation of anterior SHH expression from the Slk ZRS.
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