ArticleProceedings of the National Academy of Sciences of the United States of America2016
KCC2 rescues functional deficits in human neurons derived from patients with Rett syndrome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers, 2 of them syntheses that pooled it.
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Who cites it
136 citing papers in PubMed, 2 syntheses or guidelines pooled it, 217 citations in OpenAlex.
- The utility of animal models in hiPSC-based studies of autism spectrum disorder: a systematic review.Einstein (Sao Paulo, Brazil) · 2026Pooled it
- Engineered tissues and strategies to overcome challenges in drug development.Advanced drug delivery reviews · 2020Pooled it
- Trial
- Multi-omic spatial mapping of the human habenula defines the molecular and anatomical organization of medial and lateral subregions.bioRxiv : the preprint server for biology · 2026Article
- GABASynapse (New York, N.Y.) · 2026Review
- GABACellular and molecular neurobiology · 2026Review
- MECP2 mutations disrupt pluripotent stem cell fate through remodeling of the three-dimensional genome.Cell death & disease · 2026Article
- KCC2 activation during postnatal development alleviates long-term deficits in CDKL5-deficient mice.Experimental & molecular medicine · 2026Article
- From mice to clinical relevance: humanizing neuroscience with human-based model systems.Frontiers in cellular neuroscience · 2026Review
- Atypical case of Rett syndrome with concurrentWorld journal of clinical pediatrics · 2025Article
- Modeling the developing nervous system: a neuroscience perspective on the use of new approach methodologies in developmental neurotoxicity testing.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- Developmental dynamics of marmoset prefrontal cortical SST and PV interneuron networks highlight primate-specific features.Development (Cambridge, England) · 2025Article
- Visualizing the Cellular and Subcellular Distribution of Fms-like Tyrosine Kinase 3 (Flt3) and Other Neuronal Proteins Using Alkaline Phosphatase (AP) Immunolabeling.International journal of molecular sciences · 2025Article
- HiPSC-derived 3D neural models reveal neurodevelopmental pathomechanisms of the Cockayne Syndrome B.Cellular and molecular life sciences : CMLS · 2024Article
- Developmental dynamics of the prefrontal cortical SST and PV interneuron networks: Insights from the monkey highlight human-specific features.bioRxiv : the preprint server for biology · 2024Article
- In and out: Benchmarking in vitro, in vivo, ex vivo, and xenografting approaches for an integrative brain disease modeling pipeline.Stem cell reports · 2024Review
- In vitro human cell culture models in a bench-to-bedside approach to epilepsy.Epilepsia open · 2024Review
- Review
- Unraveling the socio-cognitive consequences of KCC2 disruption in zebrafish: implications for neurodevelopmental disorders and therapeutic interventions.Frontiers in molecular neuroscience · 2024Article
- The function ofFrontiers in cellular neuroscience · 2024Review
76 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Rett syndrome is a severe form of autism spectrum disorder, mainly caused by mutations of a single gene methyl CpG binding protein 2 (MeCP2) on the X chromosome. Patients with Rett syndrome exhibit a period of normal development followed by regression of brain function and the emergence of autistic behaviors. However, the mechanism behind the delayed onset of symptoms is largely unknown. Here we demonstrate that neuron-specific K(+)-Cl(-) cotransporter2 (KCC2) is a critical downstream gene target of MeCP2. We found that human neurons differentiated from induced pluripotent stem cells from patients with Rett syndrome showed a significant deficit in KCC2 expression and consequently a delayed GABA functional switch from excitation to inhibition. Interestingly, overexpression of KCC2 in MeCP2-deficient neurons rescued GABA functional deficits, suggesting an important role of KCC2 in Rett syndrome. We further identified that RE1-silencing transcriptional factor, REST, a neuronal gene repressor, mediates the MeCP2 regulation of KCC2. Because KCC2 is a slow onset molecule with expression level reaching maximum later in development, the functional deficit of KCC2 may offer an explanation for the delayed onset of Rett symptoms. Our studies suggest that restoring KCC2 function in Rett neurons may lead to a potential treatment for Rett syndrome.
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