scholarly journals Slit proteins are not dominant chemorepellents for olfactory tract and spinal motor axons

Development ◽  
2001 ◽  
Vol 128 (24) ◽  
pp. 5031-5037
Author(s):  
Kalpana Patel ◽  
Julia A. B. Nash ◽  
Akira Itoh ◽  
Zhe Liu ◽  
Vasi Sundaresan ◽  
...  
Keyword(s):  
Axon Guidance ◽  
Neuronal Cell ◽  
Collagen Gel ◽  
Floor Plate ◽  
Retinal Ganglion ◽  
Motor Axons ◽  
Olfactory Tract ◽  
Spinal Motor ◽  
Competitive Inhibitors ◽  
Extracellular Glycoproteins

Members of the Slit family are large extracellular glycoproteins that may function as chemorepellents in axon guidance and neuronal cell migration. Their actions are mediated through members of the Robo family that act as their receptors. In vertebrates, Slit causes chemorepulsion of embryonic olfactory tract, spinal motor, hippocampal and retinal ganglion cell axons. Since Slits are expressed in the septum and floor plate during the period when these tissues cause chemorepulsion of olfactory tract and spinal motor axons respectively, it has been proposed that Slits function as guidance cues. We have tested this hypothesis in collagen gel co-cultures using soluble Robo/Fc chimeras, as competitive inhibitors, to disrupt Slit interactions. We find that the addition of soluble Robo/Fc has no effect on chemorepulsion of olfactory tract and spinal motor axons when co-cultured with septum or floor plate respectively. Thus, we conclude that although Slits are expressed in the septum and floor plate, their proteins do not contribute to the major chemorepulsive activities emanating from these tissues which cause repulsion of olfactory tract and spinal motor axons.

Cranial Motor Axons Respond Differently to the Floor Plate and Sensory Ganglia in Collagen Gel Co-cultures

1996 ◽  
Vol 8 (5) ◽  
pp. 906-916 ◽  
Author(s):  
Anna Tucker ◽  
Andrew Lumsden ◽  
Sarah Guthrie
Keyword(s):  
Collagen Gel ◽  
Floor Plate ◽  
Sensory Ganglia ◽  
Motor Axons

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.

Vav2 is required for Netrin‐1 receptor‐class‐specific spinal motor axon guidance

2021 ◽  
Author(s):  
Yi‐Syue Tsou ◽  
Chih‐Yang Wang ◽  
Ming‐Yuan Chang ◽  
Tsung‐I Hsu ◽  
Meng‐Ting Wu ◽  
...  
Keyword(s):  
Axon Guidance ◽  
Motor Axon ◽  
Spinal Motor

scholarly journals Early Functional Impairment in Experimental Glaucoma Is Accompanied by Disruption of the GABAergic System and Inceptive Neuroinflammation

2021 ◽  
Vol 22 (14) ◽  
pp. 7581
Author(s):  
Oliver W. Gramlich ◽  
Cheyanne R. Godwin ◽  
David Wadkins ◽  
Benjamin W. Elwood ◽  
Markus H. Kuehn
Keyword(s):  
Axon Guidance ◽  
Gene Expression Analysis ◽  
Adenoviral Vectors ◽  
Significant Loss ◽  
Aminobutyric Acid ◽  
Complement Cascade ◽  
Retinal Ganglion ◽  
Functional Changes ◽  
Experimental Glaucoma ◽  
Iop Elevation

Glaucoma is a leading cause of irreversible blindness worldwide, and increased intraocular pressure (IOP) is a major risk factor. We aimed to determine if early functional and molecular differences in the glaucomatous retina manifest before significant retinal ganglion cell (RGC) loss is apparent. Adenoviral vectors expressing a pathogenic form of myocilin (Ad5.MYOC) were used to induce IOP elevation in C57BL/6 mice. IOP and pattern electroretinograms (pERG) were recorded, and retinas were prepared for RNA sequencing, immunohistochemistry, or to determine RGC loss. Ocular injection of Ad5.MYOC leads to reliable IOP elevation, resulting in significant loss of RGC after nine weeks. A significant decrease in the pERG amplitude was evident in eyes three weeks after IOP elevation. Retinal gene expression analysis revealed increased expression for 291 genes related to complement cascade, inflammation, and antigen presentation in hypertensive eyes. Decreased expression was found for 378 genes associated with the γ-aminobutyric acid (GABA)ergic and glutamatergic systems and axon guidance. These data suggest that early functional changes in RGC might be due to reduced GABAA receptor signaling and neuroinflammation that precedes RGC loss in this glaucoma model. These initial changes may offer new targets for early detection of glaucoma and the development of new interventions.

scholarly journals Ephexin1 Is Required for Eph-Mediated Limb Trajectory of Spinal Motor Axons

2018 ◽  
Vol 38 (8) ◽  
pp. 2043-2056 ◽  
Author(s):  
Chih-Ju Chang ◽  
Ming-Yuan Chang ◽  
Szu-Yi Chou ◽  
Chi-Chen Huang ◽  
Jian-Ying Chuang ◽  
...  
Keyword(s):  
Motor Axons ◽  
Spinal Motor

scholarly journals Regulation of axon repulsion by MAX-1 SUMOylation and AP-3

2018 ◽  
Vol 115 (35) ◽  
pp. E8236-E8245
Author(s):  
Shih-Yu Chen ◽  
Chun-Ta Ho ◽  
Wei-Wen Liu ◽  
Mark Lucanic ◽  
Hsiu-Ming Shih ◽  
...  
Keyword(s):  
Axon Guidance ◽  
Neural Development ◽  
Biochemical Analysis ◽  
Genetic Interaction ◽  
Motor Axons ◽  
Surface Receptors ◽  
C Elegans ◽  
Guidance Receptors ◽  
Axon Repulsion

During neural development, growing axons express specific surface receptors in response to various environmental guidance cues. These axon guidance receptors are regulated through intracellular trafficking and degradation to enable navigating axons to reach their targets. In Caenorhabditis elegans, the UNC-5 receptor is necessary for dorsal migration of developing motor axons. We previously found that MAX-1 is required for UNC-5–mediated axon repulsion, but its mechanism of action remained unclear. Here, we demonstrate that UNC-5–mediated axon repulsion in C. elegans motor axons requires both max-1 SUMOylation and the AP-3 complex β subunit gene, apb-3. Genetic interaction studies show that max-1 is SUMOylated by gei-17/PIAS1 and acts upstream of apb-3. Biochemical analysis suggests that constitutive interaction of MAX-1 and UNC-5 receptor is weakened by MAX-1 SUMOylation and by the presence of APB-3, a competitive interactor with UNC-5. Overexpression of APB-3 reroutes the trafficking of UNC-5 receptor into the lysosome for protein degradation. In vivo fluorescence recovery after photobleaching experiments shows that MAX-1 SUMOylation and APB-3 are required for proper trafficking of UNC-5 receptor in the axon. Our results demonstrate that SUMOylation of MAX-1 plays an important role in regulating AP-3–mediated trafficking and degradation of UNC-5 receptors during axon guidance.

Expression of a lacZ transgene reveals floor plate cell morphology and macromolecular transfer to commissural axons

Development ◽  
1993 ◽  
Vol 119 (4) ◽  
pp. 1217-1228 ◽  
Author(s):  
R.M. Campbell ◽  
A.C. Peterson
Keyword(s):  
Neural Tube ◽  
Neuronal Cell ◽  
Floor Plate ◽  
Ventral Midline ◽  
Ample Evidence ◽  
Commissural Axons ◽  
Neuronal Cell Bodies ◽  
Lateral Branches ◽  
And Function ◽  
Beta Galactosidase

The floor plate is situated at the ventral midline of the neural tube and is an important intermediate target for commissural axons. During elongation, these axons converge bilaterally on the ventral midline neural tube and after crossing the floor plate make an abrupt rostral turn. Ample evidence indicates that the initial projection of commissural axons to the floor plate is guided by a chemotropic factor secreted by floor plate cells. However, the way in which the subsequent interaction of these axons with the floor plate leads them to make further trajectory changes remains undefined. In an effort to gain further understanding of the structure and function of floor plate cells, we have taken advantage of a line of transgenic mice in which these cells express beta-galactosidase and thus can be stained by histochemical means. In this line, a genomic imprinting mechanism restricts the expression of the lacZ transgene to only a proportion of the floor plate cells, allowing their morphology to be appreciated with particular clarity. Our analysis revealed that the basal processes of floor plate cells are flattened in their rostrocaudal dimension and possess fine lateral branches which are aligned with commissural axons. Unexpectedly, beta-galactosidase activity was also detected within longer transverse linear profiles traversing the floor plate whose ultrastructural appearance was not that of floor plate cells but instead corresponded to that of commissural axons. Enzyme activity was not detected in more proximal axonal segments or in the neuronal cell bodies from which these axons originated. Therefore, we propose that the transgene product, and potentially other proteins synthesized by floor plate cells, can be transferred to decussating axons.

scholarly journals The endosomal sorting adaptor HD-PTP is required for ephrin-B:EphB signalling in cellular collapse and spinal motor axon guidance

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sylvie Lahaie ◽  
Daniel Morales ◽  
Halil Bagci ◽  
Noumeira Hamoud ◽  
Charles-Etienne Castonguay ◽  
...  
Keyword(s):  
Axon Guidance ◽  
Motor Axon ◽  
Endosomal Sorting ◽  
Spinal Motor
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