ArticleProceedings of the National Academy of Sciences of the United States of America2015
Inversion of Sonic hedgehog action on its canonical pathway by electrical activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- Desert Hedgehog mediates stem Leydig cell differentiation through Ptch2/Gli1/Sf1 signaling axis.eLife · 2026Article
- GLI3 in cancer: a context-dependent regulator with diagnostic, prognostic, and therapeutic potential.Frontiers in immunology · 2026Review
- Deciphering the Calcium Code: A Review of Calcium Activity Analysis Methods Employed to Identify Meaningful Activity in Early Neural Development.Biomolecules · 2024Review
- Bioelectric networks: the cognitive glue enabling evolutionary scaling from physiology to mind.Animal cognition · 2023Review
- Calcium dynamics at the neural cell primary cilium regulate Hedgehog signaling-dependent neurogenesis in the embryonic neural tube.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A Potent Antagonist of Smoothened in Hedgehog Signaling for Epilepsy.International journal of molecular sciences · 2022Article
- Review
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- A Computational Approach to Explaining Bioelectrically Induced Persistent, Stochastic Changes of Axial Polarity in Planarian Regeneration.Bioelectricity · 2022Article
- Article
- Contribution of Smoothened Receptor Signaling in GABAergic Neurotransmission and Chloride Homeostasis in the Developing Rodent Brain.Frontiers in physiology · 2021Review
- Smoothened receptor signaling regulates the developmental shift of GABA polarity in rat somatosensory cortex.Journal of cell science · 2020Article
- Ptch2/Gas1 and Ptch1/Boc differentially regulate Hedgehog signalling in murine primordial germ cell migration.Nature communications · 2020Article
- Toward Decoding Bioelectric Events in Xenopus Embryogenesis: New Methodology for Tracking Interplay Between Calcium and Resting Potentials In Vivo.Journal of molecular biology · 2020Article
- From Neural Tube Formation Through the Differentiation of Spinal Cord Neurons: Ion Channels in Action During Neural Development.Frontiers in molecular neuroscience · 2020Article
- Sonic Hedgehog Signaling Agonist (SAG) Triggers BDNF Secretion and Promotes the Maturation of GABAergic Networks in the Postnatal Rat Hippocampus.Frontiers in cellular neuroscience · 2020Article
- Bioelectrical controls of morphogenesis: from ancient mechanisms of cell coordination to biomedical opportunities.Current opinion in genetics & development · 2019Review
- Growth at Cold Temperature Increases the Number of Motor Neurons to Optimize Locomotor Function.Current biology : CB · 2019Article
- The body electric 2.0: recent advances in developmental bioelectricity for regenerative and synthetic bioengineering.Current opinion in biotechnology · 2018Review
- NMDA Receptor Signaling Is Important for Neural Tube Formation and for Preventing Antiepileptic Drug-Induced Neural Tube Defects.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Sonic hedgehog (Shh) is a morphogenic protein that operates through the Gli transcription factor-dependent canonical pathway to orchestrate normal development of many tissues. Because aberrant levels of Gli activity lead to a wide spectrum of diseases ranging from neurodevelopmental defects to cancer, understanding the regulatory mechanisms of Shh canonical pathway is paramount. During early stages of spinal cord development, Shh specifies neural progenitors through the canonical signaling. Despite persistence of Shh as spinal cord development progresses, Gli activity is switched off by unknown mechanisms. In this study we find that Shh inverts its action on Gli during development. Strikingly, Shh decreases Gli signaling in the embryonic spinal cord by an electrical activity- and cAMP-dependent protein kinase-mediated pathway. The inhibition of Gli activity by Shh operates at multiple levels. Shh promotes cytosolic over nuclear localization of Gli2, induces Gli2 and Gli3 processing into repressor forms, and activates cAMP-responsive element binding protein that in turn represses gli1 transcription. The regulatory mechanisms identified in this study likely operate with different spatiotemporal resolution and ensure effective down-regulation of the canonical Shh signaling as spinal cord development progresses. The developmentally regulated intercalation of electrical activity in the Shh pathway may represent a paradigm for switching from canonical to noncanonical roles of developmental cues during neuronal differentiation and maturation.
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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.