Effect of polysialic acid on the behavior of retinal ganglion cell axons during growth into the optic tract and tectum

Development ◽  
1995 ◽  
Vol 121 (10) ◽  
pp. 3439-3446 ◽  
Author(s):  
X. Yin ◽  
M. Watanabe ◽  
U. Rutishauser
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Polysialic Acid ◽  
Optic Tract ◽  
Retinal Ganglion ◽  
Guidance Cues ◽  
Neural Cell Adhesion ◽  
The Central Nervous System ◽  
Optic Axons ◽  
Free Environment

We have demonstrated previously that the polysialic acid (PSA) moiety of the neural cell adhesion molecule (NCAM) can regulate peripheral nerve branching during development. In particular, it was found that specific enzymatic removal of PSA from motor axons causes them to form tight fascicles that are less responsive to normal guidance cues. In the present study, the role of PSA in the behavior of axons in the central nervous system has been examined through an analysis of chick optic axons during development. Unlike peripheral axons, which generally grow in a PSA-free environment, PSA was found to be present both on retinal ganglion cell axons and their environment in the tract and tectum. Furthermore, the enzymatic removal of PSA from the optic axons caused them to defasciculate in the tract/tectal region. This response was morphologically similar to targeting corrections made by these axons at a later stage when PSA levels have decreased, suggesting that the PSA may serve to shield them from responding prematurely to some guidance cues in their target region.

The directed growth of retinal axons towards surgically transposed tecta in Xenopus; an examination of homing behaviour by retinal ganglion cell axons

Development ◽  
1990 ◽  
Vol 108 (1) ◽  
pp. 147-158
Author(s):  
J.S. Taylor
Keyword(s):  
Ganglion Cell ◽  
Axon Guidance ◽  
Retinal Ganglion Cell ◽  
Optic Tract ◽  
Retinal Ganglion ◽  
Retinal Axons ◽  
Dorsal Neural Tube ◽  
Abnormal Structure ◽  
Optic Axons ◽  
The Brain

The growth of optic axons towards experimentally rotated tecta has been studied. In stage 24/25 embryos, a piece of the dorsal neural tube, containing the dorsal midbrain rudiment, was rotated through 180 degrees. At later stages of development, the pathways of growing optic axons were investigated by labelling with either horseradish peroxidase or fluorescent dye. It is shown that retinal ganglion cell axons followed well-defined pathways, in spite of the abnormal structure of the brain, and were able to locate displaced tecta. This directed outgrowth of retinal axons in the optic tracts appears to be related either to the tectum or to some other component included in the graft operations. In tadpoles in which the midbrain rudiment was removed, optic axons still followed the normal course of the optic tract. This observation argues against long-range target attraction as being essential in guiding growing retinal axons towards the tectum. An alternative axon guidance mechanism, selective fasciculation, is discussed as a possible alternative to explain the directed axon outgrowth which occurs in both the normal and in these experimentally manipulated tadpoles.

The metalloproteinase ADAM10 is required for retinal ganglion cell axon guidance in the developing visual systems

2007 ◽  
Vol 30 (4) ◽  
pp. 77
Author(s):  
Y. Y. Chen ◽  
C. L. Hehr ◽  
K. Atkinson-Leadbeater ◽  
J. C. Hocking ◽  
S. McFarlane
Keyword(s):  
Ganglion Cell ◽  
Axon Guidance ◽  
Retinal Ganglion Cell ◽  
Growth Cone ◽  
Expression Patterns ◽  
Optic Tract ◽  
Axon Growth ◽  
Proteolytic Processing ◽  
Retinal Ganglion

Background: The growth cone interprets cues in its environment in order to reach its target. We want to identify molecules that regulate growth cone behaviour in the developing embryo. We investigated the role of A disintegrin and metalloproteinase 10 (ADAM10) in axon guidance in the developing visual system of African frog, Xenopus laevis. Methods: We first examined the expression patterns of adam10 mRNA by in situ hybridization. We then exposed the developing optic tract to an ADAM10 inhibitor, GI254023X, in vivo. Lastly, we inhibited ADAM10 function in diencephalic neuroepithelial cells (through which retinal ganglion cell (RGC) axons extend) or RGCs by electroporating or transfecting an ADAM10 dominant negative (dn-adam10). Results: We show that adam10 mRNA is expressed in the dorsal neuroepithelium over the time RGC axons extend towards their target, the optic tectum. Second, pharmacological inhibition of ADAM10 in an in vivo exposed brain preparation causes the failure of RGC axons to recognize their target at low concentrations (0.5, 1 μM), and the failure of the axons to make a caudal turn in the mid-diencephalon at higher concentration (5 μM). Thus, ADAM10 function is required for RGC axon guidance at two key guidance decisions. Finally, molecular inhibition of ADAM10 function by electroporating dn-adam10 in the brain neuroepithelium causes defects in RGC axon target recognition (57%) and/or defects in caudal turn (12%), as seen with the pharmacological inhibitor. In contrast, molecular inhibition of ADAM10 within the RGC axons has no effect. Conclusions: These data argue strongly that ADAM10 acts cell non-autonomously within the neuroepithelium to regulate the guidance of RGC axons. This study shows for the first time that a metalloproteinase acts in a cell non-autonomous fashion to direct vertebrate axon growth. It will provide important insights into candidate molecules that could be used to reform nerve connections if destroyed because of injury or disease. References Hattori M, Osterfield M, Flanagan JG. Regulated cleavage of a contact-mediated axon repellent. Science 2000; 289(5483):1360-5. Janes PW, Saha N, Barton WA, Kolev MV, Wimmer-Kleikamp SH, Nievergall E, Blobel CP, Himanen JP, Lackmann M, Nikolov DB. Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Cell 2005; 123(2):291-304. Pan D, Rubin GM. Kuzbanian controls proteolytic processing of Notch and mediates lateral inhibition during Drosophila and vertebrate neurogenesis. Cell 1997; 90(2):271-80.

scholarly journals Decreased TNF Levels and Improved Retinal Ganglion Cell Survival in MMP-2 Null Mice Suggest a Role for MMP-2 as TNF Sheddase

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Lies De Groef ◽  
Manuel Salinas-Navarro ◽  
Griet Van Imschoot ◽  
Claude Libert ◽  
Roosmarijn E. Vandenbroucke ◽  
...  
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Retinal Ganglion ◽  
Spatiotemporal Expression ◽  
Retinal Ganglion Cell Death ◽  
The Central Nervous System ◽  
Retinal Ganglion Cell Survival ◽  
Ganglion Cell Death

Matrix metalloproteinases (MMPs) have been designated as both friend and foe in the central nervous system (CNS): while being involved in many neurodegenerative and neuroinflammatory diseases, their actions appear to be indispensable to a healthy CNS. Pathological conditions in the CNS are therefore often related to imbalanced MMP activities and disturbances of the complex MMP-dependent protease network. Likewise, in the retina, various studies in animal models and human patients suggested MMPs to be involved in glaucoma. In this study, we sought to determine the spatiotemporal expression profile of MMP-2 in the excitotoxic retina and to unravel its role during glaucoma pathogenesis. We reveal that intravitreal NMDA injection induces MMP-2 expression to be upregulated in the Müller glia. Moreover, MMP-2 null mice display attenuated retinal ganglion cell death upon excitotoxic insult to the retina, which is accompanied by normal glial reactivity, yet reduced TNF levels. Hence, we propose a novelin vivofunction for MMP-2, as an activating sheddase of tumor necrosis factor (TNF). Given the pivotal role of TNF as a proinflammatory cytokine and neurodegeneration-exacerbating mediator, these findings generate important novel insights into the pathological processes contributing to glaucomatous neurodegeneration and into the interplay of neuroinflammation and neurodegeneration in the CNS.

Retinal Ganglion Cell Axon Wiring Establishing the Binocular Circuit

2020 ◽  
Vol 6 (1) ◽  
pp. 215-236
Author(s):  
Carol Mason ◽  
Nefeli Slavi
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Molecular Mechanisms ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Optic Tract ◽  
Optic Chiasm ◽  
Retinal Ganglion ◽  
Temporal Features ◽  
Ipsilateral Projection

Binocular vision depends on retinal ganglion cell (RGC) axon projection either to the same side or to the opposite side of the brain. In this article, we review the molecular mechanisms for decussation of RGC axons, with a focus on axon guidance signaling at the optic chiasm and ipsi- and contralateral axon organization in the optic tract prior to and during targeting. The spatial and temporal features of RGC neurogenesis that give rise to ipsilateral and contralateral identity are described. The albino visual system is highlighted as an apt comparative model for understanding RGC decussation, as albinos have a reduced ipsilateral projection and altered RGC neurogenesis associated with perturbed melanogenesis in the retinal pigment epithelium. Understanding the steps for RGC specification into ipsi- and contralateral subtypes will facilitate differentiation of stem cells into RGCs with proper navigational abilities for effective axon regeneration and correct targeting of higher-order visual centers.

Sign in / Sign up

Export Citation Format

Share Document