Appearance of target-specific guidance information for regenerating axons after CNS lesions

Wizenmann, Andrea; Thies, Edda; Klostermann, Stefan; Bonhoeffer, Friedrich; Bähr, Mathias

doi:10.1016/0896-6273(93)90126-c

Cited by 127 publications

(97 citation statements)

References 27 publications

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“…This suggests that pioneering fibers of the optic projection may not be guided by CSs, but that with increasing complexity of the differentiating brain, this cue becomes important for the developing optic projection. The optic projection of fish grows throughout life (Meyer, 1978;Marcus et al, 1999), correlated with the constitutive expression of positive (netrin-1; Petrausch et al, 2000) and negative (ephrin-A2 and -A5; C. G. guidance cues in the adult that are developmentally downregulated in mammals (Wizenmann et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Repellent Guidance of Regenerating Optic Axons by Chondroitin Sulfate Glycosaminoglycans in Zebrafish

Becker

2002

J. Neurosci.

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We analyzed the role of chondroitin sulfate (CS) glycosaminoglycans, putative inhibitors of axonal regeneration in mammals, in the regenerating visual pathway of adult zebrafish. In the adult, CS immunoreactivity was not detectable before or after an optic nerve crush in the optic nerve and tract but was constitutively present in developing and adult nonretinorecipient pretectal brain nuclei, where CSs may form a boundary preventing regenerating optic fibers from growing into these inappropriate locations. Enzymatic removal of CSs by chondroitinase ABC after optic nerve crush significantly increased the number of animals showing erroneous growth of optic axons into the nonretinorecipient magnocellular superficial/ posterior pretectal nucleus (83% vs 42% in controls). In vitro, a substrate border of CSs, but not heparan sulfates, strongly repelled regenerating retinal axons from adult zebrafish. We conclude that CSs contribute to repellent axon guidance during regeneration of the optic projection in zebrafish.

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Section: Discussionmentioning

confidence: 99%

Repellent Guidance of Regenerating Optic Axons by Chondroitin Sulfate Glycosaminoglycans in Zebrafish

Becker

2002

J. Neurosci.

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“…As shown previously, the guiding activities of deafferented colliculi are not significantly affected by time left for recovery. Thus, there was no difference in SCs 2 weeks or 2 months after optic nerve lesion (Wizenmann et al, 1993). Therefore, we pooled the colliculi of rats deafferented at different times before the membrane preparation.…”

Section: Methodsmentioning

confidence: 99%

“…For membrane preparations (Walter et al, 1987a as modified by Wizenmann et al, 1993), embryonic (E16 -E18), normal, deafferented adult rat superior, or adult rat inferior colliculi (14 -60 d after contralateral optic nerve axotomy) was used. As shown previously, the guiding activities of deafferented colliculi are not significantly affected by time left for recovery.…”

Section: Methodsmentioning

confidence: 99%

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Retinal Ganglion Cell Axons Recognize Specific Guidance Cues Present in the Deafferented Adult Rat Superior Colliculus

Bähr

Wizenmann

1996

J. Neurosci.

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During development, retinal ganglion cell axons establish a topographically ordered projection from the retina to the superior colliculus (SC). The putative guidance activities for retinal axons that operate during embryonic development are not detectable in the normal adult SC. However, these cues reappear upon transection of the optic nerve of adult rats. In the present study, we used a modified version of the "stripe assay," in which membranes from either anterior or posterior SC alternated with laminin stripes. Temporal embryonic retinal axons consistently avoid membranes from embryonic posterior SC, but only rarely from adult deafferented SC. However, they are attracted to membranes from both embryonic and adult deafferented anterior SC. Nasal retinal axons only show a significant preference for membranes from posterior SC after deafferentation. When retinal axons were offered a choice to grow on membranes either from their embryonic or their deafferented target regions, they showed a preference for the deafferented SC. On carpets consisting of laminin and membranes from normal SC (not deafferented) or nontarget regions (inferior colliculus), temporal and nasal axons grow either in a random fashion or show preferences for the laminin stripes.Our modified version of the classic stripe assay shows specific growth preferences of embryonic retinal axons for membrane lanes from their appropriate embryonic or deafferented adult target regions. These findings suggest that the deafferentation of the SC in adult rats triggers the reexpression of specific guidance activities for retinal axons. Those "attractive" guidance cues appear to be differentially expressed in the developing and deafferented SC. Key words: retina; retinotectal system; development; retinal ganglion cell; stripe assay; guiding cuesThe retinotectal projection has been widely used as a model to examine the mechanisms that underlie the formation of precise topographic patterns. During development of the rat visual system, a topographic retinotectal projection is formed: retinal ganglion cell (RGC) axons from the temporal retina project to the anterior (rostral) superior colliculus (SC), whereas nasal retinal axons project to the posterior (caudal) SC. Ventrally and dorsally located RGCs establish a similar projection along the mediolateral axis of the SC. To analyze the role of putative molecules involved in axonal guidance and target recognition, Walter et al. (1987a) developed an in vitro assay (stripe assay). In this assay, retinal axons were grown on carpets, which consist of alternating stripes of membranes derived from anterior and posterior embryonic tectum (Walter et al., 1987a,b).In all tested species (chick, mouse, fish, and rat), temporal retinal axons avoid growing on membrane stripes from the posterior SC, whereas nasal retinal axons did not show a growth preference (Walter et al., 1987a,b;Godement and Bonhoeffer, 1989;Vielmetter and Stuermer, 1989;Roskies and O'Leary, 1994). Using this assay, two different membrane-bound putative guidi...

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“…Within the target`stop-or docking-signals' are necessary to arrest the homecoming axons at the appropriate target neurons. A well-studied example of such a docking mechanism is the retinotectal projection, in which molecules that specify the anteriorposterior tectal axis for ®bers of the temporal retina are reexpressed upon denervation in the adult superior colliculus (Holt and Harris, 1993;Wizenmann et al, 1993). These molecules, ELF-1 (ephrin-A2) and RAGS (ephrin-A5, AL-1), are ligands for Eph-related receptor tyrosine kinases and are repellent for temporal or temporal and nasal retinal axons, respectively (Nakamoto et al, 1996;Monschau et al, 1997).…”

Section: Requirements For the Structural And Functional Recovery Of Imentioning

confidence: 99%

Experimental strategies to promote axonal regeneration after traumatic central nervous system injury

Stichel

Müller

1998

Progress in Neurobiology

123

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AbstractÐA damage or pathological process that destroys the continuity of axons in the mature central nervous system (CNS) has devastating consequences and produces lasting functional de®cits. One of the major challenges in this ®eld is to stimulate the regrowth of severed axons and reconstruction of pathways. Recent progress in molecular and cell biology has resulted in an explosion of knowledge on factors in the adult CNS being nonsupportive or even actively inhibitory to axonal regrowth. The new ®ndings have a strong impact on the development of new therapeutic concepts directed to stimulate axonal regeneration. They give rise to cautious optimism, showing that under some circumstances repair of a CNS lesion is possible. In this review the authors summarize the current knowledge on the factors and mechanisms involved in regeneration failure and provide an overview of the current therapeutic approaches that may enable eective CNS regeneration in the future. #

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Appearance of target-specific guidance information for regenerating axons after CNS lesions

Cited by 127 publications

References 27 publications

Repellent Guidance of Regenerating Optic Axons by Chondroitin Sulfate Glycosaminoglycans in Zebrafish

Repellent Guidance of Regenerating Optic Axons by Chondroitin Sulfate Glycosaminoglycans in Zebrafish

Retinal Ganglion Cell Axons Recognize Specific Guidance Cues Present in the Deafferented Adult Rat Superior Colliculus

Experimental strategies to promote axonal regeneration after traumatic central nervous system injury

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