ArticleDevelopmental dynamics : an official publication of the American Association of Anatomists2022
Downregulation of Grem1 expression in the distal limb mesoderm is a necessary precondition for phalanx development.
Article in Developmental dynamics : an official publication of the American Association of Anatomists, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 6 citations in OpenAlex.
- Integrated Genome-Wide Association Studies and Selection Signature Analysis Reveal the Genetic Architecture of the Wattle Trait in Goats.Animal genetics · 2026Article
- Endothelial PD-1 Regulates Vascular Homeostasis and Oligodendrogenesis during Brain Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The pathogenic mechanism of syndactyly type V identified in a Hoxd13Q50R knock-in mice.Bone research · 2024Article
- Integrated Analysis of Transcriptome Expression Profiles Reveals miRNA-326-NKX3.2-Regulated Porcine Chondrocyte Differentiation.International journal of molecular sciences · 2023Article
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Authors and funding
9 authors at 7 institutions in 4 countries.
Funding
Abstract
backgroundThe phalanges are the final skeletal elements to form in the vertebrate limb and their identity is regulated by signaling at the phalanx forming region (PFR) located at the tip of the developing digit ray. Here, we seek to explore the relationship between PFR activity and phalanx morphogenesis, which define the most distal limb skeletal elements, and signals associated with termination of limb outgrowth.
resultsAs Grem1 is extinguished in the distal chick limb mesoderm, the chondrogenesis marker Aggrecan is up-regulated in the metatarsals and phalanges. Fate mapping confirms that subridge mesoderm cells contribute to the metatarsal and phalanges when subridge Grem1 is down-regulated. Grem1 overexpression specifically blocks chick phalanx development by inhibiting PFR activity. PFR activity and digit development are also disrupted following overexpression of a Gli3 repressor, which results in Grem1 expression in the distal limb and downregulation of Bmpr1b.
conclusionsBased on expression and fate mapping studies, we propose that downregulation of Grem1 in the distal limb marks the transition from metatarsal to phalanx development. This suggests that downregulation of Grem1 in the distal limb mesoderm is necessary for phalanx development. Grem1 downregulation allows for full PFR activity and phalanx progenitor cell commitment to digit fate.
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