ArticleNature communications2021
RHOA signaling defects result in impaired axon guidance in iPSC-derived neurons from patients with tuberous sclerosis complex.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 48 citations in OpenAlex.
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- Retinal organoids with X-linked retinoschisis RS1 (E72K) mutation exhibit a photoreceptor developmental delay and are rescued by gene augmentation therapy.Stem cell research & therapy · 2024Article
- The role of TSC1 and TSC2 proteins in neuronal axons.Molecular psychiatry · 2024Review
- Modeling tuberous sclerosis complex with human induced pluripotent stem cells.World journal of pediatrics : WJP · 2024Review
- Epileptogenesis in tuberous sclerosis complex-related developmental and epileptic encephalopathy.Brain : a journal of neurology · 2023Review
- A whole transcriptome profiling analysis for antidepressant mechanism of Xiaoyaosan mediated synapse loss via BDNF/trkB/PI3K signal axis in CUMS rats.BMC complementary medicine and therapies · 2023Article
- Microtubule Cytoskeletal Network Alterations in a Transgenic Model of Tuberous Sclerosis Complex: Relevance to Autism Spectrum Disorders.International journal of molecular sciences · 2023Article
- Stem Cell-Based Organoid Models of Neurodevelopmental Disorders.Biological psychiatry · 2023Review
- Growth cone macropinocytosis of neurotrophin receptor and neuritogenesis are regulated by neuron navigator 1.Molecular biology of the cell · 2022Article
- Human photoreceptors switch from autonomous axon extension to cell-mediated process pulling during synaptic marker redistribution.Cell reports · 2022Article
- Mechanistic target of rapamycin signaling in human nervous system development and disease.Frontiers in molecular neuroscience · 2022Review
- Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Patients with Tuberous Sclerosis Complex (TSC) show aberrant wiring of neuronal connections formed during development which may contribute to symptoms of TSC, such as intellectual disabilities, autism, and epilepsy. Yet models examining the molecular basis for axonal guidance defects in developing human neurons have not been developed. Here, we generate human induced pluripotent stem cell (hiPSC) lines from a patient with TSC and genetically engineer counterparts and isogenic controls. By differentiating hiPSCs, we show that control neurons respond to canonical guidance cues as predicted. Conversely, neurons with heterozygous loss of TSC2 exhibit reduced responses to several repulsive cues and defective axon guidance. While TSC2 is a known key negative regulator of MTOR-dependent protein synthesis, we find that TSC2 signaled through MTOR-independent RHOA in growth cones. Our results suggest that neural network connectivity defects in patients with TSC may result from defects in RHOA-mediated regulation of cytoskeletal dynamics during neuronal development.
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