ArticleStem cells translational medicine2016
Rho Kinase Inhibition Is Essential During In Vitro Neurogenesis and Promotes Phenotypic Rescue of Human Induced Pluripotent Stem Cell-Derived Neurons With Oligophrenin-1 Loss of Function.
Article in Stem cells translational medicine, 2016. 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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15 citing papers in PubMed, 20 citations in OpenAlex.
- Architects of the Developing Brain: Cytoskeleton-Organizing Molecules in Neurodevelopmental Disorders.Cells · 2026Review
- Inhibition of repulsive guidance molecule A ameliorates diabetes-induced cognitive decline and hippocampal neurogenesis impairment in mice.Communications biology · 2025Article
- Joubert syndrome-derived induced pluripotent stem cells show altered neuronal differentiation in vitro.Cell and tissue research · 2024Article
- Altered cytoskeleton dynamics in patient-derived iPSC-based model of PCDH19 clustering epilepsy.Frontiers in cell and developmental biology · 2024Article
- Development of a Chemical Cocktail That Rescues Mouse Brain Demyelination in a Cuprizone-Induced Model.Cells · 2022Article
- Retinal Organoids and Retinal Prostheses: An Overview.International journal of molecular sciences · 2022Review
- Rho Kinases in Embryonic Development and Stem Cell Research.Archivum immunologiae et therapiae experimentalis · 2022Review
- Neuronal Cytoskeleton in Intellectual Disability: From Systems Biology and Modeling to Therapeutic Opportunities.International journal of molecular sciences · 2021Review
- Molecular Components of Store-Operated Calcium Channels in the Regulation of Neural Stem Cell Physiology, Neurogenesis, and the Pathology of Huntington's Disease.Frontiers in cell and developmental biology · 2021Review
- In Vitro Differentiation of Human Skin-Derived Cells into Functional Sensory Neurons-Like.Cells · 2020Article
- Repulsive Guidance Molecule A Suppresses Adult Neurogenesis.Stem cell reports · 2020Article
- ROCK/PKA Inhibition Rescues Hippocampal Hyperexcitability and GABAergic Neuron Alterations in a Oligophrenin-1 Knock-Out Mouse Model of X-Linked Intellectual Disability.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Intranasal Delivery of Bone Marrow Stromal Cells Preconditioned with Fasudil to Treat a Mouse Model of Parkinson's Disease.Neuropsychiatric disease and treatment · 2020Article
- Systematic Comparison of Retinal Organoid Differentiation from Human Pluripotent Stem Cells Reveals Stage Specific, Cell Line, and Methodological Differences.Stem cells translational medicine · 2019Article
- Integrated Genomic Medicine: A Paradigm for Rare Diseases and Beyond.Advances in genetics · 2017Review
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelled: Rho-GTPases have relevant functions in various aspects of neuronal development, such as differentiation, migration, and synaptogenesis. Loss of function of the oligophrenin-1 gene (OPHN1) causes X-linked intellectual disability with cerebellar hypoplasia and leads to hyperactivation of the rho kinase (ROCK) pathway. ROCK mainly acts through phosphorylation of the myosin phosphatase targeting subunit 1, triggering actin-myosin contractility. We show that during in vitro neurogenesis, ROCK activity decreases from day 10 until terminal differentiation, whereas in OPHN1-deficient human induced pluripotent stem cells (h-iPSCs), the levels of ROCK are elevated throughout differentiation. ROCK inhibition favors neuronal-like appearance of h-iPSCs, in parallel with transcriptional upregulation of nuclear receptor NR4A1, which is known to induce neurite outgrowth. This study analyzed the morphological, biochemical, and functional features of OPHN1-deficient h-iPSCs and their rescue by treatment with the ROCK inhibitor fasudil, shedding light on the relevance of the ROCK pathway during neuronal differentiation and providing a neuronal model for human OPHN1 syndrome and its treatment. SIGNIFICANCE: The analysis of the levels of rho kinase (ROCK) activity at different stages of in vitro neurogenesis of human induced pluripotent stem cells reveals that ROCK activity decreases progressively in parallel with the appearance of neuronal-like morphology and upregulation of nuclear receptor NR4A1. These results shed light on the role of the ROCK pathway during early stages of human neurogenesis and provide a neuronal stem cell-based model for the treatment of OPHN1 syndrome and other neurological disorders due to ROCK dysfunction.
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