Shared receptors in axon guidance: SAX-3/Robo signals via UNC-34/Enabled and a Netrin-independent UNC-40/DCC function

Yu, Timothy W.; Hao, Joe C.; Lim, Wendell A.; Tessier‐Lavigne, Marc; Bargmann, Cornelia I.

doi:10.1038/nn956

Cited by 143 publications

(153 citation statements)

References 49 publications

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“…Here, it should be noted that several clear examples of independent repulsive functions for Slit and Robo have been described in both C. elegans and Vertebrates (Brose and TessierLavigne, 2000;Zou et al, 2000;Stein and Tessier-Lavigne, 2001;Yu et al, 2002). Furthermore, studies in C. elegans have suggested that Slit repulsion and Netrin attraction act cooperatively during ventral guidance and that DCC/UNC-40 can actually potentiate SAX-3/Robo repulsion independently of Unc-6/Netrin (Hao et al, 2001;Yu et al, 2002).…”

Section: Independent Functions Of Netrin-fra and Slit-robo Regulate Mmentioning

confidence: 85%

Independent Functions of Slit–Robo Repulsion and Netrin–Frazzled Attraction Regulate Axon Crossing at the Midline inDrosophila

Garbe¹,

Bashaw²

2007

J. Neurosci.

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Section: Independent Functions Of Netrin-fra and Slit-robo Regulate Mmentioning

confidence: 85%

Independent Functions of Slit–Robo Repulsion and Netrin–Frazzled Attraction Regulate Axon Crossing at the Midline inDrosophila

Garbe¹,

Bashaw²

2007

J. Neurosci.

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“…Both signaling molecules act on conserved receptor systems, the activity of which is tightly regulated in a coordinated fashion (Stein and Tessier-Lavigne, 2001). Furthermore, both systems share downstream components, indicating that Netrin and Slit function is closely interwoven (Yu et al, 2002).…”

Section: Two Major Signaling Molecules Guide Commissural Growth Conesmentioning

confidence: 99%

TheDrosophilaARF6-GEF Schizo controls commissure formation by regulating Slit

2004

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The CNS of bilateral symmetric organisms is characterized by intensive contralateral axonal connections. Genetic screens in Drosophila have identified only a few genes required for guiding commissural growth cones toward and across the midline. Two evolutionarily conserved signaling molecules, Netrin and Slit, are expressed in the CNS midline cells. Netrin acts primarily as an attractive signaling cue, whereas Slit mediates repulsive functions. Here, we describe a detailed analysis of the Drosophilagene schizo, which is required for commissure formation. schizo leads to a commissural phenotype reminiscent of netrin mutant embryos. Double-mutant analyses indicate that Netrin and Schizo act independently. The schizo mutant phenotype can be suppressed by either expressing netrin in the CNS midline cells or by a reduction of the slit gene dose, indicating that the balance of attractive and repulsive signaling is impaired in schizo mutants. Overexpression of the schizo RNA in the CNS midline using the GAL4/UAS system leads to a slit phenocopy, suggesting that schizo primarily antagonizes Slit signaling. This is further supported by cell type-specific rescue experiments. The schizo gene generates at least two proteins containing a conserved Sec7 and a pleckstrin homology domain (PH) characteristic for guanine nucleotide exchange factors(GEF) acting on ARF GTPases, which are known to regulate endocytosis.In support of the notion that schizo regulates Slit expression via endocytosis, we found that block of endocytosis leads to a schizo-like phenotype. We thus propose that the balance of the two signaling cues Netrin and Slit can be regulated, controlling membrane dynamics.

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“…In Drosophila robo mutants, too many axons cross and recross the midline (5). Several molecules have been implicated in the Robo signaling pathway, including the actin binding protein Enabled (6,7), the tyrosine kinase Abelson (Abl) (6,8,9), and the Ras͞Rho GEF Son of Sevenless (10,11). Nevertheless, our understanding of the signal-transduction mechanism leading from Slit͞Robo to cytoskeleton rearrangement during repulsive axon guidance remains incomplete.…”

mentioning

confidence: 99%

Cross GTPase-activating protein (CrossGAP)/Vilse links the Roundabout receptor to Rac to regulate midline repulsion

Labrador

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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The regulators of the Rho-family GTPases, GTPase-activating proteins (GAPs) and guanine exchange factors (GEFs), play important roles in axon guidance. By means of a functional genomic study of the Rho-family GEFs and GAPs in Drosophila, we have identified a Rho-family GAP, CrossGAP (CrGAP), which is involved in Roundabout ( axon guidance ͉ GTPase-activating protein ͉ guanine nucleotide exchange factor ͉ Slit ͉ Roundabout

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Shared receptors in axon guidance: SAX-3/Robo signals via UNC-34/Enabled and a Netrin-independent UNC-40/DCC function

Cited by 143 publications

References 49 publications

Independent Functions of Slit–Robo Repulsion and Netrin–Frazzled Attraction Regulate Axon Crossing at the Midline inDrosophila

Independent Functions of Slit–Robo Repulsion and Netrin–Frazzled Attraction Regulate Axon Crossing at the Midline inDrosophila

TheDrosophilaARF6-GEF Schizo controls commissure formation by regulating Slit

Cross GTPase-activating protein (CrossGAP)/Vilse links the Roundabout receptor to Rac to regulate midline repulsion

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