ArticleDevelopment (Cambridge, England)2021
Dynamic extrinsic pacing of the HOX clock in human axial progenitors controls motor neuron subtype specification.
Article in Development (Cambridge, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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Who cites it
34 citing papers in PubMed, 60 citations in OpenAlex.
- Using human 3D organoid models to gain mechanistic insight in motor neuron diseases.Nature reviews. Neuroscience · 2026Review
- Emerging Regenerative Medicine for Spinal Cord Injury: Spinal Cord Organoids-on-a-Chip.International journal of molecular sciences · 2026Review
- Sodium Butyrate-Assisted Induction of Posterior Pre-Neural Progenitors from Pluripotent Stem Cells.International journal of molecular sciences · 2026Article
- Stem cell-based approach to identify regulatory TFs during mammalian cell differentiation.Stem cell reports · 2025Article
- Dynamical systems of fate and form in development.Seminars in cell & developmental biology · 2025Review
- DNA methylation identifies body segment origins of spinal ependymomas.Acta neuropathologica · 2025Article
- A differential requirement for ciliary transition zone proteins in human and mouse neural progenitor fate specification.Nature communications · 2025Article
- Protogenin facilitates trunk-to-tail HOX code transition via modulating GDF11/SMAD2 signaling in mammalian embryos.Communications biology · 2024Article
- HOX gene expression in the developing human spine.Nature communications · 2024Article
- Engineering a computable epiblast for in silico modeling of developmental toxicity.Reproductive toxicology (Elmsford, N.Y.) · 2024Article
- Therapeutic Transplantation of Human Central Nervous System Organoids for Neural Reconstruction.International journal of molecular sciences · 2024Review
- Self-organizing models of human trunk organogenesis recapitulate spinal cord and spine co-morphogenesis.Nature biotechnology · 2024Article
- Morphogenetic Designs, and Disease Models in Central Nervous System Organoids.International journal of molecular sciences · 2024Review
- Notch signalling influences cell fate decisions and HOX gene induction in axial progenitors.Development (Cambridge, England) · 2024Article
- Intrinsic and extrinsic cues time somite progenitor contribution to the vertebrate primary body axis.eLife · 2024Article
- Applying Spinal Cord Organoids as a quantitative approach to study the mammalian Hedgehog pathway.PloS one · 2024Article
- Zika Virus Infection Alters the Circadian Clock Expression in Human Neuronal Monolayer and Neurosphere Cultures.Cellular and molecular neurobiology · 2023Article
- Efficient generation of a self-organizing neuromuscular junction model from human pluripotent stem cells.Nature communications · 2023Article
- Spinal Cord Organoids to Study Motor Neuron Development and Disease.Life (Basel, Switzerland) · 2023Review
- Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Rostro-caudal patterning of vertebrates depends on the temporally progressive activation of HOX genes within axial stem cells that fuel axial embryo elongation. Whether the pace of sequential activation of HOX genes, the 'HOX clock', is controlled by intrinsic chromatin-based timing mechanisms or by temporal changes in extrinsic cues remains unclear. Here, we studied HOX clock pacing in human pluripotent stem cell-derived axial progenitors differentiating into diverse spinal cord motor neuron subtypes. We show that the progressive activation of caudal HOX genes is controlled by a dynamic increase in FGF signaling. Blocking the FGF pathway stalled induction of HOX genes, while a precocious increase of FGF, alone or with GDF11 ligand, accelerated the HOX clock. Cells differentiated under accelerated HOX induction generated appropriate posterior motor neuron subtypes found along the human embryonic spinal cord. The pacing of the HOX clock is thus dynamically regulated by exposure to secreted cues. Its manipulation by extrinsic factors provides synchronized access to multiple human neuronal subtypes of distinct rostro-caudal identities for basic and translational applications.This article has an associated 'The people behind the papers' interview.
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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.