ArticleThe Journal of clinical investigation2019
Sonic Hedgehog repression underlies gigaxonin mutation-induced motor deficits in giant axonal neuropathy.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Disease mutation in gigaxonin-E3 ligase recapitulates giant axonal neuropathy in mice.Acta neuropathologica communications · 2025Article
- Ubiquitin system mutations in neurological diseases.Trends in biochemical sciences · 2024Review
- Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail.Cancer research communications · 2024Article
- Intermediate filament dysregulation in astrocytes in the human disease model ofMolecular biology of the cell · 2023Article
- Zebrafish as a Model Organism for Studying Pathologic Mechanisms of Neurodegenerative Diseases and other Neural Disorders.Cellular and molecular neurobiology · 2023Review
- A multilevel screening pipeline in zebrafish identifies therapeutic drugs for GAN.EMBO molecular medicine · 2023Article
- A New Mouse Model of Giant Axonal Neuropathy with Overt Phenotypes and Neurodegeneration Driven by Neurofilament Disorganization.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Intermediate filament dysregulation and astrocytopathy in the human disease model ofbioRxiv : the preprint server for biology · 2023Article
- Alternative polyadenylation alters protein dosage by switching between intronic and 3'UTR sites.Science advances · 2023Article
- Editorial: Cytoskeletal alterations in aging and disease.Frontiers in cell and developmental biology · 2023Article
- Development of a high-throughput tailored imaging method in zebrafish to understand and treat neuromuscular diseases.Frontiers in molecular neuroscience · 2022Article
- Control of craniofacial and brain development by Cullin3-RING ubiquitin ligases: Lessons from human disease genetics.Experimental cell research · 2020Review
- The Ubiquitin Proteasome System in Neuromuscular Disorders: Moving Beyond Movement.International journal of molecular sciences · 2020Review
- Spastin mutations impair coordination between lipid droplet dispersion and reticulum.PLoS genetics · 2020Article
- Gigaxonin glycosylation regulates intermediate filament turnover and may impact giant axonal neuropathy etiology or treatmentJCI insight · 2020Article
- E3 Ubiquitin Ligases in Neurological Diseases: Focus on Gigaxonin and Autophagy.Frontiers in physiology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Growing evidence shows that alterations occurring at early developmental stages contribute to symptoms manifested in adulthood in the setting of neurodegenerative diseases. Here, we studied the molecular mechanisms causing giant axonal neuropathy (GAN), a severe neurodegenerative disease due to loss-of-function of the gigaxonin-E3 ligase. We showed that gigaxonin governs Sonic Hedgehog (Shh) induction, the developmental pathway patterning the dorso-ventral axis of the neural tube and muscles, by controlling the degradation of the Shh-bound Patched receptor. Similar to Shh inhibition, repression of gigaxonin in zebrafish impaired motor neuron specification and somitogenesis and abolished neuromuscular junction formation and locomotion. Shh signaling was impaired in gigaxonin-null zebrafish and was corrected by both pharmacological activation of the Shh pathway and human gigaxonin, pointing to an evolutionary-conserved mechanism regulating Shh signaling. Gigaxonin-dependent inhibition of Shh activation was also demonstrated in primary fibroblasts from patients with GAN and in a Shh activity reporter line depleted in gigaxonin. Our findings establish gigaxonin as a key E3 ligase that positively controls the initiation of Shh transduction, and reveal the causal role of Shh dysfunction in motor deficits, thus highlighting the developmental origin of GAN.
Indexed as
Identifiers
What OpenQuestion holds
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.