ArticlePLoS genetics2014
Sp6 and Sp8 transcription factors control AER formation and dorsal-ventral patterning in limb development.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 61 citations in OpenAlex.
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- Enhancer-directed gene delivery for digit regeneration based on conserved epidermal factors.bioRxiv : the preprint server for biology · 2025Article
- Specialized signaling centers direct cell fate and spatial organization in a mesodermal organoid model.Science advances · 2025Article
- Developmental and transcriptional programs that define the initiation of the forelimb.bioRxiv : the preprint server for biology · 2025Article
- A review of genetic variation underlying chicken phenotypic diversity.Poultry science · 2025Review
- 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
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- Single-cell census of human tooth development enables generation of human enamel.Developmental cell · 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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- Recombinant Limb Assay asFrontiers in cell and developmental biology · 2022Article
- Conserved and species-specific chromatin remodeling and regulatory dynamics during mouse and chicken limb bud development.Nature communications · 2021Article
- Activation of the WNT-BMP-FGF Regulatory Network Induces the Onset of Cell Death in Anterior Mesodermal Cells to Establish the ANZ.Frontiers in cell and developmental biology · 2021Article
- The Geometry of Limb Motor Innervation is Controlled by the Dorsal-Ventral Compartment Boundary in the Chick Limbless Mutant.Neuroscience · 2020Article
- Krüppel-like factor/specificity protein evolution in the Spiralia and the implications for cephalopod visual system novelties.Proceedings. Biological sciences · 2020Article
- A Review of the Genetics and Pathogenesis of Syndactyly in Humans and Experimental Animals: A 3-Step Pathway of Pathogenesis.BioMed research international · 2019Review
- Characterization of cis-regulatory elements for Fgf10 expression in the chick embryo.Developmental dynamics : an official publication of the American Association of Anatomists · 2018Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The formation and maintenance of the apical ectodermal ridge (AER) is critical for the outgrowth and patterning of the vertebrate limb. The induction of the AER is a complex process that relies on integrated interactions among the Fgf, Wnt, and Bmp signaling pathways that operate within the ectoderm and between the ectoderm and the mesoderm of the early limb bud. The transcription factors Sp6 and Sp8 are expressed in the limb ectoderm and AER during limb development. Sp6 mutant mice display a mild syndactyly phenotype while Sp8 mutants exhibit severe limb truncations. Both mutants show defects in AER maturation and in dorsal-ventral patterning. To gain further insights into the role Sp6 and Sp8 play in limb development, we have produced mice lacking both Sp6 and Sp8 activity in the limb ectoderm. Remarkably, the elimination or significant reduction in Sp6;Sp8 gene dosage leads to tetra-amelia; initial budding occurs, but neither Fgf8 nor En1 are activated. Mutants bearing a single functional allele of Sp8 (Sp6-/-;Sp8+/-) exhibit a split-hand/foot malformation phenotype with double dorsal digit tips probably due to an irregular and immature AER that is not maintained in the center of the bud and on the abnormal expansion of Wnt7a expression to the ventral ectoderm. Our data are compatible with Sp6 and Sp8 working together and in a dose-dependent manner as indispensable mediators of Wnt/βcatenin and Bmp signaling in the limb ectoderm. We suggest that the function of these factors links proximal-distal and dorsal-ventral patterning.
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Registered trials
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