Robos are required for the correct targeting of retinal ganglion cell axons in the visual pathway of the brain

Plachez, Céline; Andrews, William D.; Liapi, Anastasia; Knoell, Bernd; Drescher, Uwe; Mankoo, Baljinder S.; Zhe, Liu; Mambetisaeva, Elvira T.; Annan, Adelaide; Bannister, L. H.; Parnavelas, John G.; Richards, Linda J.; Sundaresan, Vasi

doi:10.1016/j.mcn.2007.12.017

Cited by 39 publications

(53 citation statements)

References 41 publications

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“…We showed previously that Hs6st1 Ϫ/Ϫ RGCs are less sensitive to Slit2's chemorepellant activity than wild type RGCs and that defects seen in the optic chiasms of Hs2st Ϫ/Ϫ and Hs6st1 Ϫ/Ϫ embryos are similar to those seen in Slit;Robo mutants (Pratt et al, 2006). Specifically, Hs6st1 Ϫ/Ϫ , Slit1 Ϫ/Ϫ ;Slit2 Ϫ/Ϫ , and Robo2 Ϫ/Ϫ embryos all have increased inter-retinal innervation while Hs2st Ϫ/Ϫ , Slit1 Ϫ/Ϫ , Slit1 Ϫ/Ϫ ;Slit2 Ϫ/Ϫ , and Robo2 Ϫ/Ϫ embryos all show ectopic wandering of axons along the midline Pratt et al, 2006;Plachez et al, 2008).…”

Section: Introductionmentioning

confidence: 57%

“…We were unable to count numbers of axons growing up the midline using this semiquantitative analysis and so we cannot formally exclude the possibility that Hs2st and Slit1 have some independent functions here as they clearly do in the preoptic area where Hs2st cannot act exclusively through Slit1 to prevent preoptic area innervation as Slit1 Ϫ/Ϫ embryos lack this phenotype ) (see Fig. 11 retina and chiasm During normal development of the optic chiasm, RGC axons are kept confined to the highly characteristic X-shaped pathway by the repulsive activities of Slit1 and Slit2, mediated through Robo2 receptors on the navigating axons Plachez et al, 2008;Thompson et al, 2009 Ϫ/Ϫ embryos, we examined expression of Robo1 and Robo2 in the retina and Slit1 and Slit2 at the optic chiasm using both in situ hybridization and qRT-PCR. Although Robo1 is not thought to play a role in normal RGC axon navigation at the optic chiasm (Plachez et al, 2008) we included Robo1 in the analysis as changes in its expression level in mutant embryos might have functional consequences.…”

Section: Green Arrow) B E H Hs6st1mentioning

confidence: 96%

“…Any additional phenotypes not seen in either single mutant would indicate functional redundancy where loss of either gene can be compensated by the activity of the other, such that the phenotype only appears when both genes are absent. We concentrated on four optic chiasm phenotypes associated with Hst and/or Slit/Robo function Pratt et al, 2006;Thompson et al, 2006;Plachez et al, 2008): (1) inter-retinal innervation (Fig 3, red arrows); (2) ectopic midline wandering (Fig. 3, black arrows); (3) ectopic growth into the preoptic area (Fig.…”

Section: Slit2mentioning

confidence: 99%

“…11 retina and chiasm During normal development of the optic chiasm, RGC axons are kept confined to the highly characteristic X-shaped pathway by the repulsive activities of Slit1 and Slit2, mediated through Robo2 receptors on the navigating axons Plachez et al, 2008;Thompson et al, 2009 Ϫ/Ϫ embryos, we examined expression of Robo1 and Robo2 in the retina and Slit1 and Slit2 at the optic chiasm using both in situ hybridization and qRT-PCR. Although Robo1 is not thought to play a role in normal RGC axon navigation at the optic chiasm (Plachez et al, 2008) we included Robo1 in the analysis as changes in its expression level in mutant embryos might have functional consequences. We analyzed E14.5 embryos, the stage at which retinal axons are navigating the optic chiasm and make abnormal decisions in Hs2st Ϫ/Ϫ and Hs6st1 Ϫ/Ϫ embryos (Pratt et al, 2006).…”

Section: Green Arrow) B E H Hs6st1mentioning

confidence: 99%

“…The axon guidance molecules Slit1 and Slit2 and their receptors Robo1 and Robo2 have context-specific roles in guiding RGC axons through the optic chiasm and callosal axons across the telencephalic midline (Erskine et al, 2000;Bagri et al, 2002;Plump et al, 2002;Shu et al, 2003b;Andrews et al, 2006;Thompson et al, 2006;Ló pez-Bendito et al, 2007;Plachez et al, 2008). We showed previously that Hs6st1 Ϫ/Ϫ RGCs are less sensitive to Slit2's chemorepellant activity than wild type RGCs and that defects seen in the optic chiasms of Hs2st Ϫ/Ϫ and Hs6st1 Ϫ/Ϫ embryos are similar to those seen in Slit;Robo mutants (Pratt et al, 2006).…”

Section: Introductionmentioning

confidence: 95%

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Heparan Sulfate Sugar Modifications Mediate the Functions ofSlitsand Other Factors Needed for Mouse Forebrain Commissure Development

Conway¹,

Howe²,

Nettleton³

et al. 2011

J. Neurosci.

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Heparan sulfate proteoglycans are cell surface and secretory proteins that modulate intercellular signaling pathways including Slit/Robo and FGF/FGFR. The heparan sulfate sugar moieties on HSPGs are subject to extensive postsynthetic modification, generating enormous molecular complexity that has been postulated to provide increased diversity in the ability of individual cells to respond to specific signaling molecules. This diversity could help explain how a relatively small number of axon guidance molecules are able to instruct the extremely complex connectivity of the mammalian brain. Consistent with this hypothesis, we previously showed that mutant mice lacking the heparan sulfotransferases (Hsts) Hs2st or Hs6st1 display major axon guidance defects at the developing optic chiasm. Here we further explore the role of these Hsts at the optic chiasm and investigate their function in corpus callosum development. Each Hst is expressed in a distinct pattern and each mutant displays a specific spectrum of axon guidance defects. Particular Hs2st ؊/؊ and Hs6st1phenotypes closely match those of Slit1 ؊/؊ and Slit2 ؊/؊ embryos respectively, suggesting possible functional relationships. To test functional interactions between Hs2st or Hs6st1 and Slits we examined optic chiasm and corpus callosum phenotypes in a panel of genotypes where Hs2st or Hs6st1 and Slit1 or Slit2 function were simultaneously reduced or absent. We find examples of Hs2st and Hs6st1 having epistatic, synergistic, and antagonistic genetic relationships with Slit1 and/or Slit2 depending on the context. At the corpus callosum we find that Hs6st1 has Slit-independent functions and our data indicate additional roles in FGF signaling.

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Section: Introductionmentioning

confidence: 57%

Section: Green Arrow) B E H Hs6st1mentioning

confidence: 96%

Section: Slit2mentioning

confidence: 99%

Section: Green Arrow) B E H Hs6st1mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

See 3 more Smart Citations

Heparan Sulfate Sugar Modifications Mediate the Functions ofSlitsand Other Factors Needed for Mouse Forebrain Commissure Development

Conway¹,

Howe²,

Nettleton³

et al. 2011

J. Neurosci.

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Cranial Pair II: The Optic Nerves

Herrera

Agudo‐Barriuso²,

Murcia‐Belmonte

2018

The Anatomical Record

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The optic nerves (ONs), one of the 12 pairs of cranial nerves (Pair II), together with the olfactory and the cochlear nerves, are devoted to transmit sensory inputs. In particular, ONs convey visual information from the retina to the brain. In mammals, the ONs are bilateral structures that extend from the optic disc to the optic chiasm containing glial cells and retinal ganglion cells (RGCs) axons. RGCs are the only retinal neurons able to collect visual information and transmit it to the visual centers in the brain for its processing and integration with the rest of sensory inputs. During embryonic development, RGCs born in the retina extend their axons to exit the eye and follow a stereotypic path outlined by the transient expression of a wide set of guidance molecules. As the rest of central nervous system structures, the ONs are covered with myelin produced by oligodendrocytes and wrapped by the meninges. ON injuries or RGCs degenerative conditions may provoke partial or complete blindness because they are incapable of spontaneous regeneration. Here, we first review major advances on the current knowledge about the mechanisms underlying the formation of the ONs in mammals. Then, we discuss some of the human disorders and pathologies affecting the development and function of the ONs and finally we comment on the existing view about ON regeneration possibilities. Anat Rec, 302:428-445, 2019.

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Repulsive axon guidance cues ephrin‐A2 and slit3 stop protrusion of the growth cone leading margin concurrently with inhibition of ADF/cofilin and ERM proteins

2012

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Axonal growth cones turn away from repulsive guidance cues. This may start with reduced protrusive motility in the region the growth cone leading margin that is closer to the source of repulsive cue. Using explants of E7 chick temporal retina, we examine the effects of two repulsive guidance cues, ephrin-A2 and slit3, on retinal ganglion cell growth cone protrusive activity, total F-actin, free F-actin barbed ends, and the activities (phosphorylation states) of actin regulatory proteins, ADF/cofilin and ERM proteins. Ephrin-A2 rapidly stops protrusive activity simultaneously with reducing F-actin, free barbed ends and the activities of ADF/cofilin and ERM proteins. Slit3 also stops protrusion and reduces the activities of ADF/cofilin and ERM proteins. We interpret these results as indicating that repulsive guidance cues inhibit actin polymerization and actin-membrane linkage to stop protrusive activity. Retrograde F-actin flow withdraws actin to the C-domain, where F-actin bundles interact with myosin II to generate contractile forces that can collapse and retract the growth cone. Our results suggest that common mechanisms are used by repulsive guidance cue to disable growth cone motility and remodel growing axon terminals.

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Robos are required for the correct targeting of retinal ganglion cell axons in the visual pathway of the brain

Cited by 39 publications

References 41 publications

Heparan Sulfate Sugar Modifications Mediate the Functions ofSlitsand Other Factors Needed for Mouse Forebrain Commissure Development

Heparan Sulfate Sugar Modifications Mediate the Functions ofSlitsand Other Factors Needed for Mouse Forebrain Commissure Development

Cranial Pair II: The Optic Nerves

Repulsive axon guidance cues ephrin‐A2 and slit3 stop protrusion of the growth cone leading margin concurrently with inhibition of ADF/cofilin and ERM proteins

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