The Neuronal Architecture of Xenopus Retinal Ganglion Cells Is Sculpted by Rho-Family GTPases In Vivo

Dendritogenesis, axonogenesis, pathfinding, and target recognition are all affected in distinct ways when Xenopus retinal ganglion cells (RGCs) are transfected with constitutively active (ca), wild-type (wt), and dominant negative (dn) Rho-family GTPases in vivo. Dendritogenesis required Rac1 and Cdc42 activity. Moreover, ca-Rac1 caused dendrite hyperproliferation. Axonogenesis, in contrast, was inhibited by ca-Rac1. This phenotype was partially rescued by the coexpression of dn cyclin-dependent kinase (Cdk5), a proposed effector of Rac1, suggesting that Rac1 activity must be regulated tightly for normal axonogenesis. Growth cone morphology was particularly sensitive to dn-RhoA and wt-Cdc42 constructs. These also caused targeting errors, such as tectal bypass, suggesting that cytoskeletal rearrangements are involved in target recognition and are transduced by these pathways.

• Publication year

  1999

• Venue

  Journal of Neuroscience

• Publication date

  1999-10-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1523/JNEUROSCI.19-19-08454.1999PMID 10493746PMCID PMC6783015
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Cytoplasmic localization of LIM-kinase 1 is directed by a short sequence within the PDZ domain.

  1998cited by this paper
• Rac1-dependent actin filament organization in growth cones is necessary for beta1-integrin-mediated advance but not for growth on poly-D-lysine.

  1998cited by this paper
• UNC-73 activates the Rac GTPase and is required for cell and growth cone migrations in C. elegans.

  1998influential reference
• The Small GTP-binding Protein Rac Promotes the Dissociation of Gelsolin from Actin Filaments in Neutrophils*

  1998cited by this paper
• Rho GTPases and the actin cytoskeleton.

  1998cited by this paper
• Overexpression of a Neural-specific Rho Family GTPase, cRac1B, Selectively Induces Enhanced Neuritogenesis and Neurite Branching in Primary Neurons

  1998influential reference
• Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase

  1998cited by this paper
• Drosophila Rac1 controls motor axon guidance.

  1998influential reference
• The p35/Cdk5 kinase is a neuron-specific Rac effector that inhibits Pak1 activity

  1998cited by this paper
• Gelsolin is a downstream effector of rac for fibroblast motility

  1998cited by this paper
• Identification of a Novel, Putative Rho-specific GDP/GTP Exchange Factor and a RhoA-binding Protein: Control of Neuronal Morphology

  1997cited by this paper
• Myosin functions in Xenopus retinal ganglion cell growth cone motility in vivo.

  1997cited by this paper
• Rho family small GTP-binding proteins in growth cone signalling

  1997cited by this paper
• Regulation of dendritic growth and remodeling by Rho, Rac, and Cdc42.

  1997cited by this paper
• p140mDia, a mammalian homolog of Drosophila diaphanous,is a target protein for Rho small GTPase and is a ligand for profilin

  1997cited by this paper
• The role of cyclin-dependent kinase 5 and a novel regulatory subunit in regulating muscle differentiation and patterning.

  1997cited by this paper
• Rho family GTPases and neuronal growth cone remodelling: relationship between increased complexity induced by Cdc42Hs, Rac1, and acetylcholine and collapse induced by RhoA and lysophosphatidic acid

  1997cited by this paper
• Rac1 Mediates Collapsin-1-Induced Growth Cone Collapse

  1997influential reference
• Rho, Rac and Cdc42 GTPases regulate the organization of the actin cytoskeleton.

  1997cited by this paper
• Regulation of Actin Polymerization in Cell-free Systems by GTPγS and Cdc42

  1997cited by this paper
• Role of a new Rho family member in cell migration and axon guidance in C. elegans.

  1997cited by this paper
• Rho family GTP-binding proteins in growth cone signalling.

  1997cited by this paper
• Differential effects of the Rac GTPase on Purkinje cell axons and dendritic trunks and spines

  1996influential reference
• Lysophosphatidic Acid‐Induced Neurite Retraction in PC12 Cells: Control by Phosphoinositide‐Ca2+ Signaling and Rho

  1996cited by this paper
• The cdk5/p35 kinase is essential for neurite outgrowth during neuronal differentiation.

  1996influential reference
• The Faciogenital Dysplasia Gene Product FGD1 Functions as a Cdc42Hs-specific Guanine-Nucleotide Exchange Factor*

  1996cited by this paper
• Cadherin function is required for axon outgrowth in retinal ganglion cells in vivo.

  1996cited by this paper
• Protein Kinase N (PKN) and PKN-Related Protein Rhophilin as Targets of Small GTPase Rho

  1996cited by this paper
• Regulation of Myosin Phosphatase by Rho and Rho-Associated Kinase (Rho-Kinase)

  1996cited by this paper
• Phosphorylation and Activation of Myosin by Rho-associated Kinase (Rho-kinase)*

  1996cited by this paper
• A role for Rac in Tiaml-induced membrane ruffling and invasion

  1995cited by this paper
• Chimeric integrins expressed in retinal ganglion cells impair process outgrowth in vivo.

  1995cited by this paper
• Inhibition of lysophosphatidate- and thrombin-induced neurite retraction and neuronal cell rounding by ADP ribosylation of the small GTP-binding protein Rho

  1994influential reference
• Distinct morphogenetic functions of similar small GTPases: Drosophila Drac1 is involved in axonal outgrowth and myoblast fusion.

  1994influential reference
• Intracellular localization of the P21rho proteins

  1992cited by this paper
• The small GTP-binding protein rac regulates growth factor-induced membrane ruffling.

  1992cited by this paper
• Bcr encodes a GTPase-activating protein for p21rac

  1991cited by this paper
• Lipofection of cDNAs in the embryonic vertebrate central nervous system.

  1990cited by this paper
• A single-cell analysis of early retinal ganglion cell differentiation in Xenopus: from soma to axon tip

  1989cited by this paper
• rac, a novel ras-related family of proteins that are botulinum toxin substrates.

  1989cited by this paper
• Expression of the ras-related ralA, rho12 and rab genes in adult mouse tissues.

  1988cited by this paper
• Retinal axons with and without their somata, growing to and arborizing in the tectum of Xenopus embryos: a time-lapse video study of single fibres in vivo.

  1987cited by this paper
• Stages in the structural differentiation of retinal ganglion cells

  1986cited by this paper
• The development of retinal ganglion cells in a tetraploid strain of Xenopus laevis: A morphological study utilizing intracellular dye injection

  1984cited by this paper
• Normal Table of Xenopus Laevis

  1968cited by this paper
• Properties and functions of the surface coat in amphibian embryos

  1943influential reference

• Exercise training promotes nerve cell repair and regeneration after spinal cord injury.

  2025cites this paper
• Endodermal cells use contact inhibition of locomotion to achieve uniform cell dispersal during zebrafish gastrulation

  2025cites this paper
• Melatonin Improves Neuroprotection and Neuroplasticity in Middle-Aged Mice Following Permanent Focal Cerebral Ischemia

  2025cites this paper
• Axonal Regeneration after Spinal Cord Injury: Molecular Mechanisms, Regulatory Pathways, and Novel Strategies

  2024cites this paper
• The small GTPase Cdc42 regulates shell field morphogenesis in a gastropod mollusk.

  2024cites this paper
• Endodermal cells use contact inhibition of locomotion to achieve uniform cell dispersal during zebrafish gastrulation

  2023cites this paper
• Trio and Kalirin as unique enactors of Rho/Rac spatiotemporal precision.

  2022cites this paper
• Regulation of dendrite growth by Cdc42 effector protein-4 in hippocampal neurons in vitro

  2022cites this paper
• Delta-Catenin as a Modulator of Rho GTPases in Neurons

  2022cites this paper
• Effects of Amyloid Precursor Protein Overexpression on NF-κB, Rho-GTPase and Pro-Apoptosis Bcl-2 Pathways in Neuronal Cells.

  2021cites this paper
• Cdc42 Facilitates Axonogenesis by Enhancing Microtubule Stabilization in Primary Hippocampal Neurons

  2021cites this paper
• Modulation of Serotonin Receptors in Neurodevelopmental Disorders: Focus on 5-HT7 Receptor

  2021cites this paper
• Cellular Mechanisms Underlying Retinoic Acid-Induced Growth Cone Guidance During Neuronal Regeneration

  2019influential citation
• The adhesion-GPCR BAI1 shapes dendritic arbors via Bcr-mediated RhoA activation causing late growth arrest

  2019cites this paper
• Rac1 Modulates Excitatory Synaptic Transmission in Mouse Retinal Ganglion Cells

  2019cites this paper
• Inhibition of Rho GTPases in Invertebrate Growth Cones Induces a Switch in Responsiveness to Retinoic Acid

  2019cites this paper
• PAR3–PAR6–atypical PKC polarity complex proteins in neuronal polarization

  2018cites this paper
• E3 Ubiquitin-Protein Ligase SMURF1 in the Nucleus Accumbens Mediates Cocaine Seeking.

  2018cites this paper
• The role of Small GTPases in Neuronal Morphogenesis and Polarity 45 Chapter 2 : The Role of Small GTPases in Neuronal Morphogenesis and Polarity

  2017cites this paper
• Defining the function of Amyloid Precursor Protein dimerisation in neuritogenesis

  2017cites this paper
• RhoA Inhibitor Treatment At Acute Phase of Spinal Cord Injury May Induce Neurite Outgrowth and Synaptogenesis*

  2017cites this paper
• CDK5 downregulation enhances synaptic plasticity

  2016cites this paper
• The Role of NADPH Oxidases in Neurite Outgrowth and Zebrafish Neurodevelopment

  2016influential citation
• BMP7‐induced dendritic growth in sympathetic neurons requires p75NTR signaling

  2016cites this paper
• A GAL4‐inducible transgenic tool kit for the in vivo modulation of Rho GTPase activity in zebrafish

  2016cites this paper
• Different roles of the small GTPases Rac1, Cdc42, and RhoG in CALEB/NGC‐induced dendritic tree complexity

  2016cites this paper
• GEFs and Rac GTPases control directional specificity of neurite extension along the anterior-posterior axis

  2016cites this paper
• GEFs and Rac GTPases control directional specificity of neurite extension along the anterior–posterior axis

  2016cites this paper
• Comparative analysis of molecular mechanism of spinal cord injury with time based on bioinformatics data

  2015cites this paper
• Pftaire1 (Cyclin Dependent Kinase14): Role and Function in Axonal Outgrowth During the development of the CNS

  2015cites this paper
• Synaptic Cytoskeletal Plasticity in the Prefrontal Cortex Following Psychostimulant Exposure

  2015cites this paper
• Intrinsic and extrinsic mechanisms of dendritic morphogenesis.

  2015cites this paper
• Rac1 plays an essential role in axon growth and guidance and in neuronal survival in the central and peripheral nervous systems

  2015cites this paper
• MECP2e1 Mutation Reduces the Dendritic Complexity of Rett Syndrome Patient iPS Cell-derived Neurons

  2014cites this paper
• MECP 2 e 1 Mutation Reduces the Dendritic Complexity of Rett Syndrome Patient iPS Cell-Derived Neurons

  2014cites this paper
• Connecting the Retina to the Brain

  2014cites this paper
• Activity-Dependent Regulation of Dendritic Complexity by Semaphorin 3A through Farp1

  2014cites this paper
• Rab5 and Rab4 Regulate Axon Elongation in the Xenopus Visual System

  2014cites this paper
• Small GTP-binding Proteins: A Future for the Treatment of Cognitive Disorders?

  2014cites this paper
• Molecular mechanisms of dendrite stability

  2013cites this paper
• Atorvastatin requires geranylgeranyl transferase-I and Rac1 activation to exert neuronal protection and induce plasticity.

  2013cites this paper
• Gene expression signature analysis and protein-protein interaction network construction of spinal cord injury.

  2013cites this paper
• Neuropeptide orphanin FQ inhibits dendritic morphogenesis through activation of RhoA

  2013cites this paper
• Changes in the GEF-H1 Pathways after Traumatic Brain Injury

  2013cites this paper
• Cell-intrinsic drivers of dendrite morphogenesis

  2013cites this paper
• Integrin α3 Is Required for Late Postnatal Stability of Dendrite Arbors, Dendritic Spines and Synapses, and Mouse Behavior

  2013cites this paper
• cofilinndent inhibition of Cdc42 and activation of Neocortical dendritic complexity is controlled during development

  2012cites this paper
• The dendritic tree and brain disorders.

  2012cites this paper
• Integrin β1 Signals through Arg to Regulate Postnatal Dendritic Arborization, Synapse Density, and Behavior

  2012cites this paper
• Integrin1SignalsthroughArgtoRegulatePostnatal DendriticArborization,SynapseDensity,andBehavior

  2012cites this paper
• NOMA-GAP-dependent inhibition of Cdc 42 and activation of cofilin Neocortical dendritic complexity is controlled during development by Material Supplemental

  2012influential citation
• A brief account of rho GTPases in retinal physiology and pathophysiology.

  2012cites this paper
• The Xenopus retinal ganglion cell as a model neuron to study the establishment of neuronal connectivity

  2012cites this paper
• Neocortical dendritic complexity is controlled during development by NOMA-GAP-dependent inhibition of Cdc42 and activation of cofilin.

  2012influential citation
• Regulation of dendritic branching by Cdc42 GAPs.

  2012cites this paper
• The role of small GTPases in neuronal morphogenesis and polarity

  2012cites this paper
• Guiding Neuronal Growth Cones by Ca 2+ Signals: During axon pathfinding in the developing nervous system, spatiotemporal patterns of Ca 2+ signals can govern growth cone extension and steering—by symmetric versus asymmetric regulation of cytoskeletal and membrane dynamics

  2011cites this paper
• Corticosterone induced morphological changes of hippocampal and amygdaloid cell lines are dependent on 5-HT7 receptor related signal pathway.

  2011cites this paper
• Fascin implements the distinction between two sensory neuron morphologies

  2011cites this paper
• Modulation of dendritic spines and synaptic function by Rac1: a possible link to Fragile X syndrome pathology.

  2011cites this paper
• A GtPase Rac1 participa da proliferação de células gliais de Müller após lesão excitotóxica.

  2011cites this paper
• BDNF-PromotedIncreasesinProximalDendritesOccurvia CREB-DependentTranscriptionalRegulationofCypin

  2011cites this paper
• Cell adhesion signaling pathways: First responders to cocaine exposure?

  2011cites this paper
• BDNF-Promoted Increases in Proximal Dendrites Occur via CREB-Dependent Transcriptional Regulation of Cypin

  2011cites this paper
• The roles of postsynaptic density-95 protein (PSD-95) and its interactor, cypin, in the regulation of microtubule organization, dendrite morphology, and neuroprotection

  2011cites this paper
• Cell adhesion signaling pathways

  2011cites this paper
• Anti-Ganglioside Antibody-Mediated Activation of RhoA Induces Inhibition of Neurite Outgrowth

  2011cites this paper
• ROCK inhibition prevents tau hyperphosphorylation and p25/CDK5 increase after global cerebral ischemia.

  2011cites this paper
• Brain‐derived neurotrophic factor and the development of structural neuronal connectivity

  2010influential citation
• RhoE stimulates neurite‐like outgrowth in PC12 cells through inhibition of the RhoA/ROCK‐I signalling

  2010cites this paper
• Spinogenesis and pruning from early visual onset to adulthood: an intracellular injection study of layer III pyramidal cells in the ventral visual cortical pathway of the macaque monkey.

  2010cites this paper
• Genes required for normal neuronal morphology in Caenorhabditis elegans

  2010cites this paper
• Mechanisms of synapse and dendrite maintenance and their disruption in psychiatric and neurodegenerative disorders.

  2010cites this paper
• CORTICOSTERONE INDUCED MORPHOLOGICAL CHANGES OF HIPPOCAMPAL AND AMYGDALOID CELL LINES ARE DEPENDENT ON 5-HT 7 RECEPTOR RELATED SIGNAL PATHWAY By

  2010cites this paper
• GTPases Rho e o potencial regenerativo da retina de mamíferos

  2010cites this paper
• Balanced Vav2 GEF activity regulates neurite outgrowth and branching in vitro and in vivo.

  2010cites this paper
• Statins decrease dendritic arborization in rat sympathetic neurons by blocking RhoA activation

  2009cites this paper
• Loss of dendrite stabilization by the Abl-related gene (Arg) kinase regulates behavioral flexibility and sensitivity to cocaine

  2009cites this paper
• The NM23 family in development

  2009cites this paper
• Endogenous Activation Patterns of Cdc42 GTPase Within Drosophila Embryos

  2009cites this paper
• LIMK1 acts downstream of BMP signaling in developing retinal ganglion cell axons but not dendrites.

  2009cites this paper
• Role of RhoA in Activity-Dependent Cortical Axon Branching

  2008cites this paper
• Enhanced Ras activity preserves dendritic size and extension as well as synaptic contacts of neurons after functional deprivation in synRas mice

  2008cites this paper
• Flamingo/Starry Night in embryonic abdominal sensory axon development of Drosophila

  2008cites this paper
• Localization of the Diaphanous-related formin Daam1 to neuronal dendrites.

  2008cites this paper
• Rho inhibition recruits DCC to the neuronal plasma membrane and enhances axon chemoattraction to netrin 1

  2008cites this paper
• Functions of Rac GTPases during Neuronal Development

  2008cites this paper
• Integrin signaling is integral to regeneration.

  2008cites this paper
• ErbB4-Neuregulin Signaling Modulates Synapse Development and Dendritic Arborization through Distinct Mechanisms*

  2008cites this paper
• Expression of Rho GTPases Rho‐A and Rac1 in the adult and developing gerbil cerebellum

  2008cites this paper
• Identification of a developmentally regulated pathway of membrane retrieval in neuronal growth cones

  2008cites this paper
• Characterization of the Role of Rac3 in Neuronal Function

  2008cites this paper
• TrkB-mediated activation of geranylgeranyltransferase I promotes dendritic morphogenesis

  2008cites this paper
• Regulation of filopodia dynamics is critical for proper synapse formation

  2008cites this paper
• p21-activated Kinase-aberrant Activation and Translocation in Alzheimer Disease Pathogenesis*

  2008cites this paper
• NF-Protocadherin and TAF1 Regulate Retinal Axon Initiation and Elongation In Vivo

  2008cites this paper
• Ena/VASP function in retinal axons is required for terminal arborization but not pathway navigation

  2007cites this paper
• Cell-Autonomous TrkB Signaling in Presynaptic Retinal Ganglion Cells Mediates Axon Arbor Growth and Synapse Maturation during the Establishment of Retinotectal Synaptic Connectivity

  2007influential citation
• Regulation of Neuronal Morphogenesis by Abl Family Kinases

  2007cites this paper
• The generation and characterization of transgenic mice expressing modifiers of Rho GTPases

  2007cites this paper