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Neurolin Ig domain 2 participates in retinal axon guidance and Ig domains 1 and 3 in fasciculation.

Leppert CA, Diekmann H, Paul C, Laessing U, Marx M, Bastmeyer M, Stuermer CA - J. Cell Biol. (1999)

Bottom Line: Repeated intraocular injections of a mAb against Ig domain 2 disturb the disk-directed growth: axons grow in aberrant routes and fail to reach the optic disk, but remain fasciculated. mAbs against Ig domains 1 and 3 disturb the formation of tight fascicles. mAb against Ig domain 2 significantly increases the incidence of growth cone departure from the disk-oriented fascicle track, while mAbs against Ig domains 1 and 3 do not.This was demonstrated by time-lapse videorecording of labeled growth cones.Thus, Ig domain 2 of neurolin is apparently essential for growth cone guidance towards the disk, presumably by being part of a receptor (or complex) for an axon guidance component.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Konstanz, D-78457 Konstanz, Germany.

ABSTRACT
The optic disk-directed growth of retinal ganglion cell axons is markedly disturbed in the presence of polyclonal antineurolin antibodies, which mildly affect fasciculation (Ott, H., M. Bastmeyer, and C.A.O. Stuermer, 1998. J. Neurosci. 18:3363-3372). New monoclonal antibodies (mAbs) against goldfish neurolin, an immunoglobulin (Ig) superfamily cell adhesion/recognition molecule with five Ig domains, were generated to assign function (guidance versus fasciculation) to specific Ig domains. By their ability or failure to recognize Chinese hamster ovary cells expressing recombinant neurolin with deletions of defined Ig domains, mAbs were identified as being directed against Ig domains 1, 2, or 3, respectively. Repeated intraocular injections of a mAb against Ig domain 2 disturb the disk-directed growth: axons grow in aberrant routes and fail to reach the optic disk, but remain fasciculated. mAbs against Ig domains 1 and 3 disturb the formation of tight fascicles. mAb against Ig domain 2 significantly increases the incidence of growth cone departure from the disk-oriented fascicle track, while mAbs against Ig domains 1 and 3 do not. This was demonstrated by time-lapse videorecording of labeled growth cones. Thus, Ig domain 2 of neurolin is apparently essential for growth cone guidance towards the disk, presumably by being part of a receptor (or complex) for an axon guidance component.

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Aberrant routes in retinae injected with mAb N518  against Ig domain 2. (A) Higher magnification of the dorsal retina shown in Fig. 4, as indicated by the box in the upper right corner. Instead of growing directly towards the optic disk (od),  young RGC axons form new subfascicles, change direction (arrows), and follow irregular pathways. (B–D) Examples of pathfinding errors. Young RGC axons depart from disk-oriented fascicles (arrow in B), grow back towards the retinal margin,  establish circular routes (arrow in C), and form subfascicles that  end in between fascicles (arrow in D). The retinal margin is up  and the optic disk down. Bars, A, 200 μm; B–D, 100 μm.
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Figure 5: Aberrant routes in retinae injected with mAb N518 against Ig domain 2. (A) Higher magnification of the dorsal retina shown in Fig. 4, as indicated by the box in the upper right corner. Instead of growing directly towards the optic disk (od), young RGC axons form new subfascicles, change direction (arrows), and follow irregular pathways. (B–D) Examples of pathfinding errors. Young RGC axons depart from disk-oriented fascicles (arrow in B), grow back towards the retinal margin, establish circular routes (arrow in C), and form subfascicles that end in between fascicles (arrow in D). The retinal margin is up and the optic disk down. Bars, A, 200 μm; B–D, 100 μm.

Mentions: After injections of mAb N518, misrouted axons were abundant in all 16 retinae. Axons in aberrant routes occurred from nasal over dorsal to temporal retinal aspects, and were most abundant in the inner retinal aspect, i.e., when axons had covered roughly 50% of their path from the periphery to the optic disk (Fig. 4). Axons that were previously associated with other axons in distinct fascicles no longer preserved this order. They formed new subfascicles with more distant axons and traveled in loops and other irregular pathways (Figs. 4 and 5). Quite frequently, axons that left their fascicle of origin grew away from the disk, turned again, associated with bundles of other misoriented or disk-oriented fascicles, or ended somewhere between other axon bundles (Fig. 5). Despite their errant path, a fraction of axons reached the optic disk (Figs. 4 and 5 A), yet others appeared to get lost (Fig. 5, A, B, and D). Most axons were able to form tight fascicles over the first 50% of the path from the margin to the disk, but even here subfascicles separated from the major fascicle (Fig. 4). These subfascicles then often followed curvy routes and crossed other fascicles until they merged again with one of the prominent bundles. Yet, as they approached the inner 50% of the retina, most axons apparently lost their ability to travel along disk-directed fascicles (Fig. 5). This suggests that many young growing axons in mAb N518-treated retinae fail to respond to guidance cues that they normally would perceive.


Neurolin Ig domain 2 participates in retinal axon guidance and Ig domains 1 and 3 in fasciculation.

Leppert CA, Diekmann H, Paul C, Laessing U, Marx M, Bastmeyer M, Stuermer CA - J. Cell Biol. (1999)

Aberrant routes in retinae injected with mAb N518  against Ig domain 2. (A) Higher magnification of the dorsal retina shown in Fig. 4, as indicated by the box in the upper right corner. Instead of growing directly towards the optic disk (od),  young RGC axons form new subfascicles, change direction (arrows), and follow irregular pathways. (B–D) Examples of pathfinding errors. Young RGC axons depart from disk-oriented fascicles (arrow in B), grow back towards the retinal margin,  establish circular routes (arrow in C), and form subfascicles that  end in between fascicles (arrow in D). The retinal margin is up  and the optic disk down. Bars, A, 200 μm; B–D, 100 μm.
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Figure 5: Aberrant routes in retinae injected with mAb N518 against Ig domain 2. (A) Higher magnification of the dorsal retina shown in Fig. 4, as indicated by the box in the upper right corner. Instead of growing directly towards the optic disk (od), young RGC axons form new subfascicles, change direction (arrows), and follow irregular pathways. (B–D) Examples of pathfinding errors. Young RGC axons depart from disk-oriented fascicles (arrow in B), grow back towards the retinal margin, establish circular routes (arrow in C), and form subfascicles that end in between fascicles (arrow in D). The retinal margin is up and the optic disk down. Bars, A, 200 μm; B–D, 100 μm.
Mentions: After injections of mAb N518, misrouted axons were abundant in all 16 retinae. Axons in aberrant routes occurred from nasal over dorsal to temporal retinal aspects, and were most abundant in the inner retinal aspect, i.e., when axons had covered roughly 50% of their path from the periphery to the optic disk (Fig. 4). Axons that were previously associated with other axons in distinct fascicles no longer preserved this order. They formed new subfascicles with more distant axons and traveled in loops and other irregular pathways (Figs. 4 and 5). Quite frequently, axons that left their fascicle of origin grew away from the disk, turned again, associated with bundles of other misoriented or disk-oriented fascicles, or ended somewhere between other axon bundles (Fig. 5). Despite their errant path, a fraction of axons reached the optic disk (Figs. 4 and 5 A), yet others appeared to get lost (Fig. 5, A, B, and D). Most axons were able to form tight fascicles over the first 50% of the path from the margin to the disk, but even here subfascicles separated from the major fascicle (Fig. 4). These subfascicles then often followed curvy routes and crossed other fascicles until they merged again with one of the prominent bundles. Yet, as they approached the inner 50% of the retina, most axons apparently lost their ability to travel along disk-directed fascicles (Fig. 5). This suggests that many young growing axons in mAb N518-treated retinae fail to respond to guidance cues that they normally would perceive.

Bottom Line: Repeated intraocular injections of a mAb against Ig domain 2 disturb the disk-directed growth: axons grow in aberrant routes and fail to reach the optic disk, but remain fasciculated. mAbs against Ig domains 1 and 3 disturb the formation of tight fascicles. mAb against Ig domain 2 significantly increases the incidence of growth cone departure from the disk-oriented fascicle track, while mAbs against Ig domains 1 and 3 do not.This was demonstrated by time-lapse videorecording of labeled growth cones.Thus, Ig domain 2 of neurolin is apparently essential for growth cone guidance towards the disk, presumably by being part of a receptor (or complex) for an axon guidance component.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Konstanz, D-78457 Konstanz, Germany.

ABSTRACT
The optic disk-directed growth of retinal ganglion cell axons is markedly disturbed in the presence of polyclonal antineurolin antibodies, which mildly affect fasciculation (Ott, H., M. Bastmeyer, and C.A.O. Stuermer, 1998. J. Neurosci. 18:3363-3372). New monoclonal antibodies (mAbs) against goldfish neurolin, an immunoglobulin (Ig) superfamily cell adhesion/recognition molecule with five Ig domains, were generated to assign function (guidance versus fasciculation) to specific Ig domains. By their ability or failure to recognize Chinese hamster ovary cells expressing recombinant neurolin with deletions of defined Ig domains, mAbs were identified as being directed against Ig domains 1, 2, or 3, respectively. Repeated intraocular injections of a mAb against Ig domain 2 disturb the disk-directed growth: axons grow in aberrant routes and fail to reach the optic disk, but remain fasciculated. mAbs against Ig domains 1 and 3 disturb the formation of tight fascicles. mAb against Ig domain 2 significantly increases the incidence of growth cone departure from the disk-oriented fascicle track, while mAbs against Ig domains 1 and 3 do not. This was demonstrated by time-lapse videorecording of labeled growth cones. Thus, Ig domain 2 of neurolin is apparently essential for growth cone guidance towards the disk, presumably by being part of a receptor (or complex) for an axon guidance component.

Show MeSH
Related in: MedlinePlus