Functional neural circuits depend on the establishment of specific connections between neurons and their target cells. To this end, many axons have to travel long distances to reach their target cells during development. Studies addressing the molecular mechanisms of axon guidance have to overcome the complexity of subpopulation-specific requirements with respect to pathways, guidance cues, and target recognition. Compared to the brain, the relatively simple structure of the spinal cord provides an advantage for experimental studies of axon guidance mechanisms. Therefore, the so far best understood model for axon guidance is the dI1 population of dorsal interneurons of the spinal cord. They extend their axons ventrally towards the floor plate. After midline crossing, they turn rostrally along the contralateral floor-plate border. Despite the fact that the trajectory of dI1 axons seems to be rather simple, the number of axon guidance molecules involved in the decisions taken by these axons is bewildering. Because guidance molecules and mechanisms are conserved throughout the developing nervous system, we can generalize what we have learned about the navigation of the floor plate as an intermediate target for commissural axons to the brain.
Calsyntenins form a family of linker proteins between distinct populations of vesicles and kinesin motors for axonal transport. They were implicated in synapse formation and synaptic plasticity by findings in worms, mice and humans. These findings were in accordance with the postsynaptic localization of the Calsyntenins in the adult brain. However, they also affect the formation of neural circuits, as loss of Calsyntenin-1 (Clstn1) was shown to interfere with axonal branching and axon guidance. Despite the fact that Calsyntenins were discovered originally in embryonic chicken motoneurons, their distribution in the developing nervous system has not been analyzed in detail so far. Here, we summarize our analysis of the temporal and spatial expression patterns of the cargo-docking proteins Clstn1, Clstn2 and Clstn3 during neural development by comparing the dynamic distribution of their mRNAs by in situ hybridization in the spinal cord, the cerebellum, the retina and the tectum, as well as in the dorsal root ganglia (DRG).
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