Regulation of Rho Family GTPases Is Required to Prevent Axons from Crossing the Midline

Fritz, Janice L.; VanBerkum, Mark F. A.

doi:10.1006/dbio.2002.0842

Cited by 36 publications

(41 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is seen for loss of Rac1/Mtl double mutants, and even more so for Rac1/Rac2/Mtl triple mutants in the Drosophila visual system, with local disruptions in topographic mapping and frequent misrouting of photoreceptor axons around and beyond the medulla (Hakeda-Suzuki et al 2002). In agreement with these findings, interfering with Rac function by expressing DN Rac1 results in a bypass phenotype in the Drosophila giant fiber system (Allen et al 2000), CNS (Fritz and VanBerkum 2002), and motor axons (Kaufmann et al 1998;. Conversely, expression of wild-type or CA Rac1 can cause the premature termination or stalling of axons in the Drosophila giant fiber system (Allen et al 2000) and in Purkinje cells of CA Rac1 transgenic mice (Luo et al 1996a).…”

Section: The Role Of Rho Signaling In Axon Guidancementioning

confidence: 52%

The role of the Rho GTPases in neuronal development

Govek¹,

Newey²,

Aelst³

2005

Genes Dev.

893

799

View full text Add to dashboard Cite

Our brain serves as a center for cognitive function and neurons within the brain relay and store information about our surroundings and experiences. Modulation of this complex neuronal circuitry allows us to process that information and respond appropriately. Proper development of neurons is therefore vital to the mental health of an individual, and perturbations in their signaling or morphology are likely to result in cognitive impairment. The development of a neuron requires a series of steps that begins with migration from its birth place and initiation of process outgrowth, and ultimately leads to differentiation and the formation of connections that allow it to communicate with appropriate targets. Over the past several years, it has become clear that the Rho family of GTPases and related molecules play an important role in various aspects of neuronal development, including neurite outgrowth and differentiation, axon pathfinding, and dendritic spine formation and maintenance. Given the importance of these molecules in these processes, it is therefore not surprising that mutations in genes encoding a number of regulators and effectors of the Rho GTPases have been associated with human neurological diseases. This review will focus on the role of the Rho GTPases and their associated signaling molecules throughout neuronal development and discuss how perturbations in Rho GTPase signaling may lead to cognitive disorders.

show abstract

Section: The Role Of Rho Signaling In Axon Guidancementioning

confidence: 52%

The role of the Rho GTPases in neuronal development

Govek¹,

Newey²,

Aelst³

2005

Genes Dev.

893

799

View full text Add to dashboard Cite

show abstract

“…Robo also interacts with the Rac/Cdc42 GAP, CrGAP/Vilse, and both RNAi and gain-of-function experiments indicate that regulation of Rac activity by both GEFs and GAPs is necessary for proper Robo signaling (Hu et al 2005). Consistent with an active role for Rho in Slit-dependent repulsion, DN-DRho enhances and CA-DRho suppress midline-crossing defects caused by homozygous loss of Sos in Drosophila CNS (Fritz and VanBerkum 2002). In contrast to this, overexpression of the Rho GEF GEF64C results in too many axons crossing the midline, similar to the Robo loss-of-function phenotype.…”

Section: Other Guidance Cuesmentioning

confidence: 89%

Rho and Ras GTPases in Axon Growth, Guidance, and Branching

Hall¹,

Lalli²

2010

Cold Spring Harbor Perspectives in Biology

378

355

View full text Add to dashboard Cite

The establishment of precise neuronal cell morphology provides the foundation for all aspects of neurobiology. During development, axons emerge from cell bodies after an initial polarization stage, elongate, and navigate towards target regions guided by a range of environmental cues. The Rho and Ras families of small GTPases have emerged as critical players at all stages of axonogenesis. Their ability to coordinately direct multiple signal transduction pathways with precise spatial control drives many of the activities that underlie this morphogenetic program: the dynamic assembly, disassembly, and reorganization of the actin and microtubule cytoskeletons, the interaction of the growing axon with other cells and extracellular matrix, the delivery of lipids and proteins to the axon through the exocytic machinery, and the internalization of membrane and proteins at the leading edge of the growth cone through endocytosis. This article highlights the contribution of Rho and Ras GTPases to axonogenesis.

show abstract

“…Although positive roles for GTPases in commissure formation in the Drosophila embryo have not been directly demonstrated, trio (in this study) and GEF64C, a Rho GEF (Bashaw et al, 2001), interact genetically with fra leading to the dramatic disruption of commissures. Additionally, expression of constitutively active or dominantly negative isoforms of both Rac and Rho, as well as constitutively active Cdc42, causes axons to cross the CNS midline inappropriately (Fan et al, 2003;Fritz and VanBerkum, 2002;Matsuura et al, 2004). Recent studies have implicated Cdc42 and Rac1/CED-10 as effectors of DCC and UNC-40 signaling, but the biochemical mechanisms by which GTPases are regulated have been elusive (Gitai et al, 2003;Li et al, 2002a;Li et al, 2002b;Shekarabi and Kennedy, 2002).…”

Section: Discussionmentioning

confidence: 99%

The Abelson tyrosine kinase, the Trio GEF and Enabled interact with the Netrin receptor Frazzled in Drosophila

et al. 2005

View full text Add to dashboard Cite

The attractive Netrin receptor Frazzled (Fra), and the signaling molecules Abelson tyrosine kinase (Abl), the guanine nucleotide-exchange factor Trio, and the Abl substrate Enabled (Ena), all regulate axon pathfinding at the Drosophila embryonic CNS midline. We detect genetic and/or physical interactions between Fra and these effector molecules that suggest that they act in concert to guide axons across the midline. Mutations in Abl and trio dominantly enhance fra and Netrin mutant CNS phenotypes, and fra;Abl and fra;trio double mutants display a dramatic loss of axons in a majority of commissures. Conversely, heterozygosity for ena reduces the severity of the CNS phenotype in fra, Netrin and trio,Abl mutants. Consistent with an in vivo role for these molecules as effectors of Fra signaling, heterozygosity for Abl, trio or ena reduces the number of axons that inappropriately cross the midline in embryos expressing the chimeric Robo-Fra receptor. Fra interacts physically with Abl and Trio in GST-pulldown assays and in co-immunoprecipitation experiments. In addition, tyrosine phosphorylation of Trio and Fra is elevated in S2 cells when Abl levels are increased. Together, these data suggest that Abl, Trio, Ena and Fra are integrated into a complex signaling network that regulates axon guidance at the CNS midline.

show abstract

Regulation of Rho Family GTPases Is Required to Prevent Axons from Crossing the Midline

Cited by 36 publications

References 61 publications

The role of the Rho GTPases in neuronal development

The role of the Rho GTPases in neuronal development

Rho and Ras GTPases in Axon Growth, Guidance, and Branching

The Abelson tyrosine kinase, the Trio GEF and Enabled interact with the Netrin receptor Frazzled in Drosophila

Contact Info

Product

Resources

About