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The L1 cell adhesion molecule is essential for topographic mapping of retinal axons.

ABSTRACT: The retinocollicular projection is a preferred axon guidance pathway for investigating molecular mechanisms of synaptic targeting in the mammalian CNS. Here we identify a previously unrecognized role of the L1 cell adhesion molecule in topographic mapping of retinal ganglion cell (RGC) axons to their targets in the mouse superior colliculus (SC). L1 was transiently expressed on RGC axons during axon growth and targeting. DiI labeling of retinal axons revealed that temporal axons of L1-minus mice bypassed correct target locations in the anterior SC, forming termination zones at incorrect posterior sites, which were often skewed along the mediolateral axis. During development of the retinotopic map L1-minus temporal axons extended across the anteroposterior axis of the SC like wild-type axons but failed to arborize at normal anterior target sites. L1-minus RGC axons exhibited normal crossing at the optic chiasm and fasciculation of the optic nerve. Results suggest that retinal axons require the function of L1 in addition to repellent EphA guidance receptors to achieve proper topographic mapping.

SUBMITTER: Demyanenko GP

PROVIDER: S-EPMC6741870 | biostudies-literature | 2003 Jan

REPOSITORIES: biostudies-literature

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The L1 cell adhesion molecule is essential for topographic mapping of retinal axons.

Demyanenko Galina P GP Maness Patricia F PF

The Journal of neuroscience : the official journal of the Society for Neuroscience 20030101 2

The retinocollicular projection is a preferred axon guidance pathway for investigating molecular mechanisms of synaptic targeting in the mammalian CNS. Here we identify a previously unrecognized role of the L1 cell adhesion molecule in topographic mapping of retinal ganglion cell (RGC) axons to their targets in the mouse superior colliculus (SC). L1 was transiently expressed on RGC axons during axon growth and targeting. DiI labeling of retinal axons revealed that temporal axons of L1-minus mice ...[more]

PMID: 12533613

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Project description:BackgroundLong-distance axonal growth relies on the precise interplay of guidance cues and cell adhesion molecules. While guidance cues provide positional and directional information for the advancing growth cone, cell adhesion molecules are essential in enabling axonal advancement. Such a dependence on adhesion as well as guidance molecules can be well observed in dorsal commissural interneurons, which follow a highly stereotypical growth and guidance pattern. The mechanisms and molecules involved in the attraction and outgrowth towards the ventral midline, the axon crossing towards the contralateral side, the rostral turning after midline crossing as well as the guidance along the longitudinal axis have been intensely studied. However, little is known about molecules that provide the basis for commissural axon growth along the anterior-posterior axis.ResultsMDGA2, a recently discovered cell adhesion molecule of the IgCAM superfamily, is highly expressed in dorsolaterally located (dI1) spinal interneurons. Functional studies inactivating MDGA2 by RNA interference (RNAi) or function-blocking antibodies demonstrate that either treatment results in a lack of commissural axon growth along the longitudinal axis. Moreover, results from RNAi experiments targeting the contralateral side together with binding studies suggest that homophilic MDGA2 interactions between ipsilaterally projecting axons and post-crossing commissural axons may be the basis of axonal growth along the longitudinal axis.ConclusionsDirected axonal growth of dorsal commissural interneurons requires an elaborate mixture of instructive (guidance) and permissive (outgrowth supporting) molecules. While Wnt and Sonic hedgehog (Shh) signalling pathways have been shown to specify the growth direction of post-crossing commissural axons, our study now provides evidence that homophilic MDGA2 interactions are essential for axonal extension along the longitudinal axis. Interestingly, so far each part of the complex axonal trajectory of commissural axons uses its own set of guidance and growth-promoting molecules, possibly explaining why such a high number of molecules influencing the growth pattern of commissural interneurons has been identified.

Project description:The close homolog of L1 (CHL1) is a cell adhesion molecule involved in regulation of neuronal differentiation and survival, neurite outgrowth and axon guidance during development. In the mature nervous system, CHL1 regulates synaptic activity and plasticity. The aim of the present study was to evaluate the influence of CHL1 on peripheral nerve regeneration after trauma. Using the established model of mouse femoral nerve regeneration, CHL1 knock-out mice were investigated in comparison to the wild type littermates. First, non-injured mice of both genotypes were compared regarding the synaptic phenotypes in the corresponding spinal cord segment. While no differences in phenotypes were detectable in the femoral nerve, corresponding segments in the spinal cord were observed to differ in that inhibitory perisomatic innervation of motor neurons was increased in CHL1-deficient mice, and numbers of perisomatic cholinergic synapses on motor neuronal somata were reduced. Regarding the femoral nerve after injury, CHL1-deficient mice demonstrated preferential motor axon regrowth into the saphenous vs. quadriceps branch after nerve transection upstream of the nerve bifurcation by 8 weeks after transection, indicating decreased preferential motor re-innervation. Furthermore, in injured wild-type mice, enhanced CHL1 expression was observed in regenerating axons in the proximal nerve stump upstream of the bifurcation at days 1, 3, 5, 7 and 14, and in the distal stump at days 7 and 14 after injury, when compared to non-injured mice. Injury-related upregulation of CHL1 expression was more pronounced in axons than in Schwann cells. Despite a more pronounced capacity for preferential motor axon regrowth in wild-type vs. mutant mice, only a tendency for difference in recovery of motor functions was observed between genotypes, without statistical significance Taken together, these results indicate that CHL1 is involved in peripheral nerve regeneration, because it guides regrowing axons into the appropriate nerve branch and regulates synaptic coverage in the spinal cord.

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The L1 cell adhesion molecule is essential for topographic mapping of retinal axons.

Publications

The L1 cell adhesion molecule is essential for topographic mapping of retinal axons.

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