ReviewJournal of Zhejiang University. Science. B
Apical ectodermal ridge regulates three principal axes of the developing limb.
Review in Journal of Zhejiang University. Science. B. 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, 23 citations in OpenAlex.
- Generation of Budoids: 3D Multilineage Limb Models From Mouse Embryonic Stem Cells.Bio-protocol · 2026Article
- Permissive and instructiveeLife · 2026Article
- Craniofacial endotype of obstructive sleep apnea: Spatial matrix hypothesis.Sleep & breathing = Schlaf & Atmung · 2026Review
- Evolutionary pathway and genetic mechanisms of fin-to-limb transition in vertebrates.Frontiers in cell and developmental biology · 2026Review
- Neural crest cell recruitment and reprogramming as central drivers of embryonic limb regeneration.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The TBXT Gene and Brachyury Protein Are Differentially Expressed During the Early Embryonic Development of Hu and Hulunbuir Sheep.Life (Basel, Switzerland) · 2025Article
- Cells of all trades - on the importance of spatial positioning of senescent cells in development, healing and aging.FEBS letters · 2025Review
- miR-144-3p targeting FLRT3 in osteogenic differentiation of mandibular bone marrow mesenchymal stem cells.Human genomics · 2025Article
- Adaptive evolution ofZoological research · 2025Article
- Polymelia and concurrent intestinal duplication and cloacal atresia in a broiler chick: case report and literature review.Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc · 2024Review
- Morphogens in the evolution of size, shape and patterning.Development (Cambridge, England) · 2024Review
- Lgr6-expressing functional nail stem-like cells differentiated from human-induced pluripotent stem cells.PloS one · 2024Article
- Multi-species atlas resolves an axolotl limb development and regeneration paradox.Nature communications · 2023Article
- Prenatal radiographic evaluation of congenital transverse limb deficiencies: A scoping review.World journal of orthopedics · 2023Article
- Regeneration enhancers: a field in development.American journal of physiology. Cell physiology · 2022Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding limb development not only gives insights into the outgrowth and differentiation of the limb, but also has clinical relevance. Limb development begins with two paired limb buds (forelimb and hindlimb buds), which are initially undifferentiated mesenchymal cells tipped with a thickening of the ectoderm, termed the apical ectodermal ridge (AER). As a transitional embryonic structure, the AER undergoes four stages and contributes to multiple axes of limb development through the coordination of signalling centres, feedback loops, and other cell activities by secretory signalling and the activation of gene expression. Within the scope of proximodistal patterning, it is understood that while fibroblast growth factors (FGFs) function sequentially over time as primary components of the AER signalling process, there is still no consensus on models that would explain proximodistal patterning itself. In anteroposterior patterning, the AER has a dual-direction regulation by which it promotes the sonic hedgehog (Shh) gene expression in the zone of polarizing activity (ZPA) for proliferation, and inhibits Shh expression in the anterior mesenchyme. In dorsoventral patterning, the AER activates Engrailed-1 (En1) expression, and thus represses Wnt family member 7a (Wnt7a) expression in the ventral ectoderm by the expression of Fgfs, Sp6/8, and bone morphogenetic protein (Bmp) genes. The AER also plays a vital role in shaping the individual digits, since levels of Fgf4/8 and Bmps expressed in the AER affect digit patterning by controlling apoptosis. In summary, the knowledge of crosstalk within AER among the three main axes is essential to understand limb growth and pattern formation, as the development of its areas proceeds simultaneously.
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Registered trials
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.