ArticleeNeuro
Crucial Role of Rapgef2 and Rapgef6, a Family of Guanine Nucleotide Exchange Factors for Rap1 Small GTPase, in Formation of Apical Surface Adherens Junctions and Neural Progenitor Development in the Mouse Cerebral Cortex.
Article in eNeuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Genetic marker analysis of RAPGEF6 gene and covariance structure modelling for egg.BMC genomics · 2026Article
- High Throughput Characterization of Eukaryotic 2A-Like Peptides Identifies Novel Leucine-Associated Reduction in Protein Abundance.bioRxiv : the preprint server for biology · 2026Article
- A de novo Loss-of-function Variant in RAPGEF6 Supports its Role in Neuropsychiatric Disorders.Journal of molecular neuroscience : MN · 2026Article
- Rare heterozygous de novo variants in RAPGEF2 are associated with a neurodevelopmental disorder.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- A comparative analysis of mutational profiles between triple-negative breast cancer and non-triple-negative breast cancer.Discover oncology · 2026Article
- Beer Intake is Positively, While Cheese and Dried Fruit Intake Are Negatively Genetically Correlated with Psoriasis: A GWAS Summary-Statistics Study Using condFDR/conjFDR.Clinical, cosmetic and investigational dermatology · 2026Article
- RAPGEF6 is a key biomarker with temporal characteristics in sepsis and exacerbates inflammation and oxidative stress by NF-κB-mediated necroptosis.Functional & integrative genomics · 2025Article
- A PDZ-RapGEF promotes synaptic development in Caenorhabditis elegans through a Rap/Rac signaling pathway.Development (Cambridge, England) · 2025Article
- RAPIDASH: Tag-free enrichment of ribosome-associated proteins reveals composition dynamics in embryonic tissue, cancer cells, and macrophages.Molecular cell · 2024Article
- Interactions between Ras and Rap signaling pathways during neurodevelopment in health and disease.Frontiers in molecular neuroscience · 2024Review
- RAPIDASH: A tag-free enrichment of ribosome-associated proteins reveals compositional dynamics in embryonic tissues and stimulated macrophages.bioRxiv : the preprint server for biology · 2023Article
- PXF-1 promotes synapse development at the neuromuscular junction inFrontiers in molecular neuroscience · 2022Article
- High Concentration of an ISS-N1-Targeting Antisense Oligonucleotide Causes Massive Perturbation of the Transcriptome.International journal of molecular sciences · 2021Article
- DSCAM regulates delamination of neurons in the developing midbrain.Science advances · 2020Article
- Phosphatidic acid-dependent localization and basal de-phosphorylation of RA-GEFs regulate lymphocyte trafficking.BMC biology · 2020Article
- ECE2 regulates neurogenesis and neuronal migration during human cortical development.EMBO reports · 2020Article
- Novel Polymorphisms inGenes · 2019Article
- The Sema3A receptor Plexin-A1 suppresses supernumerary axons through Rap1 GTPases.Scientific reports · 2018Article
- Comprehensive behavioral analysis of mice deficient in Rapgef2 and Rapgef6, a subfamily of guanine nucleotide exchange factors for Rap small GTPases possessing the Ras/Rap-associating domain.Molecular brain · 2018Article
- De novo and inherited private variants in MAP1B in periventricular nodular heterotopia.PLoS genetics · 2018Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cerebral neocortex development in mammals requires highly orchestrated events involving proliferation, differentiation, and migration of neural progenitors and neurons. Rapgef2 and Rapgef6 constitute a unique family of guanine nucleotide exchange factors for Rap1 small GTPase, which is known to play crucial roles in migration of postmitotic neurons. We previously reported that conditional knockout of Rapgef2 in dorsal telencephalon (Rapgef2-cKO) resulted in the formation of an ectopic cortical mass (ECM) resembling that of subcortical band heterotopia. Here we show that double knockout of Rapgef6 in Rapgef2-cKO mice (Rapgef2/6-dKO) results in marked enlargement of the ECM. While Rapgef2-cKO affects late-born neurons only, Rapgef2/6-dKO affects both early-born and late-born neurons. The Rapgef2-cKO cortex at embryonic day (E) 15.5, and the Rapgef2/6-dKO cortex at E13.5 and E15.5 show disruption of the adherens junctions (AJs) on the apical surface, detachment of radial glial cells (RGCs) from the apical surface and disorganization of the radial glial fiber system, which are accompanied by aberrant distribution of RGCs and intermediate progenitors, normally located in the ventricular zone and the subventricular zone, respectively, over the entire cerebral cortex. Moreover, intrauterine transduction of Cre recombinase into the Rapgef2(flox/flox) brains also results in the apical surface AJ disruption and the RGC detachment from the apical surface, both of which are effectively suppressed by cotransduction of the constitutively active Rap1 mutant Rap1(G12V). These results demonstrate a cell-autonomous role of the Rapgef2/6-Rap1 pathway in maintaining the apical surface AJ structures, which is necessary for the proper development of neural progenitor cells.
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