ArticleNature communications2021
Dissection of the Fgf8 regulatory landscape by in vivo CRISPR-editing reveals extensive intra- and inter-enhancer redundancy.
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 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Cis-regulatory evolution shapes facial diversity in birds and mammals.Science advances · 2026Article
- Chromatin spatial analysis by METALoci unveils sex-determining 3D regulatory hubs.Nature structural & molecular biology · 2026Article
- Enhancer-dependent gene regulation in space, time, and malignancies.International journal of cancer · 2026Review
- Enhancer Trajectories in Lineage Commitment: Regulatory Logic of States and Cooperation.Biomolecules · 2026Review
- Functional architecture of cardiac TF regulatory landscapes in control of mammalian heart development.bioRxiv : the preprint server for biology · 2025Article
- Neanderthal-derived variants increase SOX9 enhancer activity in craniofacial progenitors that shape jaw development.Development (Cambridge, England) · 2025Article
- Aberrant Enhancer Regulation, Phase Separation, and Autoimmune Diseases.Clinical reviews in allergy & immunology · 2025Review
- Evolution of cetacean-specific conserved non-coding elements suggests their role in the limb changes during secondary aquatic adaptation.BMC biology · 2025Article
- A suite of enhancer AAVs and transgenic mouse lines for genetic access to cortical cell types.Cell · 2025Article
- A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival.Nature communications · 2024Article
- A suite of enhancer AAVs and transgenic mouse lines for genetic access to cortical cell types.bioRxiv : the preprint server for biology · 2024Article
- Genomic context sensitizes regulatory elements to genetic disruption.Molecular cell · 2024Article
- Genomic context sensitizes regulatory elements to genetic disruption.bioRxiv : the preprint server for biology · 2024Article
- The Density of Regulatory Information Is a Major Determinant of Evolutionary Constraint on Noncoding DNA in Drosophila.Molecular biology and evolution · 2024Article
- Revisiting the development of cerebellar inhibitory interneurons in the light of single-cell genetic analyses.Histochemistry and cell biology · 2024Review
- Super-enhancers include classical enhancers and facilitators to fully activate gene expression.Cell · 2023Article
- Cell-specific and shared regulatory elements control a multigene locus active in mammary and salivary glands.Nature communications · 2023Article
- Decoding enhancer complexity with machine learning and high-throughput discovery.Genome biology · 2023Review
- Combinatorial effects on gene expression at the Lbx1/Fgf8 locus resolve split-hand/foot malformation type 3.Nature communications · 2023Article
- The GRN concept as a guide for evolutionary developmental biology.Journal of experimental zoology. Part B, Molecular and developmental evolution · 2023Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Developmental genes are often regulated by multiple elements with overlapping activity. Yet, in most cases, the relative function of those elements and their contribution to endogenous gene expression remain poorly characterized. An example of this phenomenon is that distinct sets of enhancers have been proposed to direct Fgf8 in the limb apical ectodermal ridge and the midbrain-hindbrain boundary. Using in vivo CRISPR/Cas9 genome engineering, we functionally dissect this complex regulatory ensemble and demonstrate two distinct regulatory logics. In the apical ectodermal ridge, the control of Fgf8 expression appears distributed between different enhancers. In contrast, we find that in the midbrain-hindbrain boundary, one of the three active enhancers is essential while the other two are dispensable. We further dissect the essential midbrain-hindbrain boundary enhancer to reveal that it is also composed by a mixture of essential and dispensable modules. Cross-species transgenic analysis of this enhancer suggests that its composition may have changed in the vertebrate lineage.
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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.