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CRMP2 and CRMP4 are required for the formation of commissural tracts in the developing zebrafish forebrain

Guo Y, Oliveros CF, Ohshima T
Dev Neurobiol. 2022 Aug 5. doi: 10.1002/dneu.22897. Online ahead of print
Axonal connections between the two sides of the brain are essential for processing sensorimotor functions, especially in animals with bilateral symmetry. The anterior commissure and post-optic commissure are two crucial axonal projections that develop early in the zebrafish central nervous system. In this study, we characterized the function of collapsin response mediator protein 2 (CRMP2) and CRMP4 in patterning the development of the anterior and post-optic commissures by analyzing morpholino-knockdown zebrafish morphants and CRISPR/Cas9-edited gene-knockout mutants. We observed a loss of commissural structures or a significant reduction in axon bundles connecting the two hemispheres, but the defects could be largely recovered by co-injecting CRMP2 or CRMP4 mRNA. Loss of both CRMP2 and CRMP4 function resulted in a synergistic increase in the number of commissural defects. To elucidate the mechanism by which CRMP2 and CRMP4 provide guidance cues for the development of the anterior and post-optic commissures, we included neuropilin 1a (Nrp1a) morphants and double morphants (CRMP2/Nrp1a and CRMP4/Nrp1a) for analysis. Our experimental results indicated that CRMP2 and CRMP4 might mediate their activities through the common semaphorin 3/Nrp1a signaling pathway.
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