ArticleNature2014
Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 125 citations in OpenAlex.
- Heterochronic limb patterning in marsupials reveals flexibility in the processes underlying lateral plate mesoderm morphogenesis.Science advances · 2026Article
- Evolution of limb and digit identity genes since the tetrapod ancestor.Nature communications · 2026Article
- Parallels in the regulatory landscape of dimorphic female and male genital structures in Drosophila melanogaster.Genetics · 2026Article
- GliFHV mice: a tool to investigate GLI processing and localization.Development (Cambridge, England) · 2025Article
- Dual Bmp-negative feedback loops modulate function of both AER and ZPA to buffer and constrain postaxial digit number.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Generation of Hoxa11-3XFLAG and Hoxd11-3XFLAG alleles to investigate Hox11 genome-wide binding.Developmental biology · 2025Article
- WNT signaling coordinately controls mouse limb bud outgrowth and establishment of the digit-interdigit pattern.Development (Cambridge, England) · 2025Article
- Epigenomic signatures of cis-regulatory elements in the developing mouse and pig forelimb.Scientific data · 2025Article
- Humerus shape evolved in cetaceans under relaxed selection and random drift.Communications biology · 2025Article
- Single-cell profiling of penta- and tetradactyl mouse limb buds identifies mesenchymal progenitors controlling digit numbers and identities.Nature communications · 2025Article
- Anterior-posterior constraint on Hedgehog signaling by hhip in teleost fin elaboration.Development (Cambridge, England) · 2024Article
- A dominant missense variant within LMBR1 related to equine polydactyly.Communications biology · 2024Article
- Morphogens in the evolution of size, shape and patterning.Development (Cambridge, England) · 2024Review
- Perspectives on Principles of Cellular Behavior from the Biophysics of Protists.Integrative and comparative biology · 2023Review
- Developmental regulation of conserved non-coding element evolution provides insights into limb loss in squamates.Science China. Life sciences · 2023Article
- Induction of kidney-related gene programs through co-option of SALL1 in mole ovotestes.Development (Cambridge, England) · 2023Article
- 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
- Article
- Distinct patterning responses of wing and leg neuromuscular systems to different preaxial polydactylies.Frontiers in cell and developmental biology · 2023Article
- Evolutionary genetics of flipper forelimb and hindlimb loss from limb development-related genes in cetaceans.BMC genomics · 2022Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 5 institutions in 5 countries.
Funding
Abstract
The large spectrum of limb morphologies reflects the wide evolutionary diversification of the basic pentadactyl pattern in tetrapods. In even-toed ungulates (artiodactyls, including cattle), limbs are adapted for running as a consequence of progressive reduction of their distal skeleton to symmetrical and elongated middle digits with hoofed phalanges. Here we analyse bovine embryos to establish that polarized gene expression is progressively lost during limb development in comparison to the mouse. Notably, the transcriptional upregulation of the Ptch1 gene, which encodes a Sonic hedgehog (SHH) receptor, is disrupted specifically in the bovine limb bud mesenchyme. This is due to evolutionary alteration of a Ptch1 cis-regulatory module, which no longer responds to graded SHH signalling during bovine handplate development. Our study provides a molecular explanation for the loss of digit asymmetry in bovine limb buds and suggests that modifications affecting the Ptch1 cis-regulatory landscape have contributed to evolutionary diversification of artiodactyl limbs.
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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.