ArticleNature communications2021
Spatial regulation by multiple Gremlin1 enhancers provides digit development with cis-regulatory robustness and evolutionary plasticity.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 38 citations in OpenAlex.
- A Twist1-regulated distal enhancer crucial for Alx1 gene expression and function during craniofacial development.Developmental biology · 2026Article
- Evolution of limb and digit identity genes since the tetrapod ancestor.Nature communications · 2026Article
- Combined mutations of hoxa13a, hoxa13b, and hoxd13a lead to structural shifts in zebrafish soft fin rays providing insight into spiny ray evolution.PLoS genetics · 2026Article
- Temporal constraints on enhancer usage shape the regulation of limb gene transcription.Nature communications · 2026Article
- Oogenesis and germinal bed morphology of the brown anole (A. sagrei).Developmental dynamics : an official publication of the American Association of Anatomists · 2026Article
- Evolutionary pathway and genetic mechanisms of fin-to-limb transition in vertebrates.Frontiers in cell and developmental biology · 2026Review
- Evolution of repressive sequences within an enhancer contributed to morphological diversity in crucifer plants.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Functional architecture of cardiac TF regulatory landscapes in control of mammalian heart development.bioRxiv : the preprint server for biology · 2025Article
- Oogenesis and germinal bed morphology of the brown anole (bioRxiv : the preprint server for biology · 2025Article
- Evolution of cetacean-specific conserved non-coding elements suggests their role in the limb changes during secondary aquatic adaptation.BMC biology · 2025Article
- WNT signaling coordinately controls mouse limb bud outgrowth and establishment of the digit-interdigit pattern.Development (Cambridge, England) · 2025Article
- Article
- Epigenomic signatures of cis-regulatory elements in the developing mouse and pig forelimb.Scientific data · 2025Article
- Convergent evolution of noncoding elements associated with short tarsus length in birds.BMC biology · 2025Article
- Single-cell profiling of penta- and tetradactyl mouse limb buds identifies mesenchymal progenitors controlling digit numbers and identities.Nature communications · 2025Article
- A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival.Nature communications · 2024Article
- TBX3 is essential for establishment of the posterior boundary of anterior genes and upregulation of posterior genes together with HAND2 during the onset of limb bud development.Development (Cambridge, England) · 2024Article
- Tgfbr1 controls developmental plasticity between the hindlimb and external genitalia by remodeling their regulatory landscape.Nature communications · 2024Article
- The BAF chromatin complex component SMARCC1 does not mediate GLI transcriptional repression of Hedgehog target genes in limb buds.Developmental biology · 2023Article
- Developmental regulation of conserved non-coding element evolution provides insights into limb loss in squamates.Science China. Life sciences · 2023Article
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Authors and funding
15 authors at 7 institutions in 5 countries.
Funding
Abstract
Precise cis-regulatory control of gene expression is essential for normal embryogenesis and tissue development. The BMP antagonist Gremlin1 (Grem1) is a key node in the signalling system that coordinately controls limb bud development. Here, we use mouse reverse genetics to identify the enhancers in the Grem1 genomic landscape and the underlying cis-regulatory logics that orchestrate the spatio-temporal Grem1 expression dynamics during limb bud development. We establish that transcript levels are controlled in an additive manner while spatial regulation requires synergistic interactions among multiple enhancers. Disrupting these interactions shows that altered spatial regulation rather than reduced Grem1 transcript levels prefigures digit fusions and loss. Two of the enhancers are evolutionary ancient and highly conserved from basal fishes to mammals. Analysing these enhancers from different species reveal the substantial spatial plasticity in Grem1 regulation in tetrapods and basal fishes, which provides insights into the fin-to-limb transition and evolutionary diversification of pentadactyl 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.