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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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Time-lapse sequence of an axon after mAb N518 injections. A DiO-labeled growth cone (arrow in A) elongates towards the optic disk (to the lower right) in association with other  labeled axons of the same fascicle (arrowhead in A). This growth  cone left its fascicle (arrow in B), turned away from the optic disk  (C–E), turned again, and continued to grow outside the fascicle  (arrow in F). Elapsed time is given in hours and minutes in the  lower right corner. Bar, 20 μm.
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Figure 8: Time-lapse sequence of an axon after mAb N518 injections. A DiO-labeled growth cone (arrow in A) elongates towards the optic disk (to the lower right) in association with other labeled axons of the same fascicle (arrowhead in A). This growth cone left its fascicle (arrow in B), turned away from the optic disk (C–E), turned again, and continued to grow outside the fascicle (arrow in F). Elapsed time is given in hours and minutes in the lower right corner. Bar, 20 μm.

Mentions: Some growth cones were videorecorded for up to 24 h to directly visualize the development of the aberrant routes. The growth cone (Fig. 8) left its fascicle of origin, turned away from the direction of the optic disk, coursed towards the periphery, turned again, and continued to grow outside of the fascicles. Its further growth could not be followed because continuous observation of labeled growth cones causes photodamage and eventually leads to the cessation of growth and disintegration of the growth cone and axon. This growth cone is a representative example of how the many abnormal routes develop after neurolin Fab and mAb N518 injections.


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)

Time-lapse sequence of an axon after mAb N518 injections. A DiO-labeled growth cone (arrow in A) elongates towards the optic disk (to the lower right) in association with other  labeled axons of the same fascicle (arrowhead in A). This growth  cone left its fascicle (arrow in B), turned away from the optic disk  (C–E), turned again, and continued to grow outside the fascicle  (arrow in F). Elapsed time is given in hours and minutes in the  lower right corner. Bar, 20 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2132892&req=5

Figure 8: Time-lapse sequence of an axon after mAb N518 injections. A DiO-labeled growth cone (arrow in A) elongates towards the optic disk (to the lower right) in association with other labeled axons of the same fascicle (arrowhead in A). This growth cone left its fascicle (arrow in B), turned away from the optic disk (C–E), turned again, and continued to grow outside the fascicle (arrow in F). Elapsed time is given in hours and minutes in the lower right corner. Bar, 20 μm.
Mentions: Some growth cones were videorecorded for up to 24 h to directly visualize the development of the aberrant routes. The growth cone (Fig. 8) left its fascicle of origin, turned away from the direction of the optic disk, coursed towards the periphery, turned again, and continued to grow outside of the fascicles. Its further growth could not be followed because continuous observation of labeled growth cones causes photodamage and eventually leads to the cessation of growth and disintegration of the growth cone and axon. This growth cone is a representative example of how the many abnormal routes develop after neurolin Fab and mAb N518 injections.

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