ArticleNeural development2012
RabGDI controls axonal midline crossing by regulating Robo1 surface expression.
Article in Neural development, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 67 citations in OpenAlex.
- Gene expression programs underlying spinal commissural neuron differentiation and axon growth across the midline.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- miR-219a-Robo1 axis acts as a conserved switch for slit-mediated commissural axon guidance.iScience · 2025Article
- The Slit-Robo signalling pathway in nervous system development: a comparative perspective from vertebrates and invertebrates.Open biology · 2025Review
- A global gene regulatory program and its region-specific regulator partition neurons into commissural and ipsilateral projection types.Science advances · 2024Article
- Cables1 links Slit/Robo and Wnt/Frizzled signaling in commissural axon guidance.Development (Cambridge, England) · 2023Article
- Article
- Structure and evolution of neuronal wiring receptors and ligands.Developmental dynamics : an official publication of the American Association of Anatomists · 2023Review
- Intracellular Trafficking Mechanisms that Regulate Repulsive Axon Guidance.Neuroscience · 2023Review
- Axon guidance at the spinal cord midline-A live imaging perspective.The Journal of comparative neurology · 2021Article
- Article
- Revisiting and refining roles of neural guidance cues in circuit assembly.Current opinion in neurobiology · 2021Review
- Dorsal commissural axon guidance in the developing spinal cord.Current topics in developmental biology · 2021Review
- Article
- Molecular mechanisms regulating axon responsiveness at the midline.Developmental biology · 2020Article
- Commissural axon guidance in the developing spinal cord: from Cajal to the present day.Neural development · 2019Review
- Temporal regulation of axonal repulsion by alternative splicing of a conserved microexon in mammalianeLife · 2019Article
- A crucial role for Arf6 in the response of commissural axons to Slit.Development (Cambridge, England) · 2019Article
- Midline axon guidance in the Drosophila embryonic central nervous system.Seminars in cell & developmental biology · 2019Review
- ADP-ribosylation factor-like 4A interacts with Robo1 to promote cell migration by regulating Cdc42 activation.Molecular biology of the cell · 2019Article
- Fibroblast growth factor receptor 1 signaling transcriptionally regulates the axon guidance cue slit1.Cellular and molecular life sciences : CMLS · 2018Article
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAxons navigate to their future synaptic targets with the help of choice points, intermediate targets that express axon guidance cues. Once they reach a choice point, axons need to switch their response from attraction to repulsion in order to move on with the next stage of their journey. The mechanisms underlying the change in axonal responsiveness are poorly understood. Commissural axons become sensitive to the repulsive activity of Slits when they cross the ventral midline of the CNS. Responsiveness to Slits depends on surface expression of Robo receptors. In Drosophila, Commissureless (Comm) plays a crucial regulatory role in midline crossing by keeping Robo levels low on precommissural axons. Interestingly, to date no vertebrate homolog of comm has been identified. Robo3/Rig1 has been shown to control Slit sensitivity before the midline, but without affecting Robo1 surface expression.
resultsWe had identified RabGDI, a gene linked to human mental retardation and an essential component of the vesicle fusion machinery, in a screen for differentially expressed floor-plate genes. Downregulation of RabGDI by in ovo RNAi caused commissural axons to stall in the floor plate, phenocopying the effect observed after downregulation of Robo1. Conversely, premature expression of RabGDI prevented commissural axons from entering the floor plate. Furthermore, RabGDI triggered Robo1 surface expression in cultured commissural neurons. Taken together, our results identify RabGDI as a component of the switching mechanism that is required for commissural axons to change their response from attraction to repulsion at the intermediate target.
conclusionRabGDI takes over the functional role of fly Comm by regulating the surface expression of Robo1 on commissural axons in vertebrates. This in turn allows commissural axons to switch from attraction to repulsion at the midline of the spinal cord.
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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.