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Contributed by Mu-ming Poo, May 30, 2013 (sent for review May 1, 2013)
Significance
Two hemispheres of the neocortex are connected via a large axon bundle, the corpus callosum (CC). Axons from one side of the cortex project primarily to the equivalent cortical area on the contralateral side. How this homotopic axon projection is achieved during development remains unclear. Quantitative analysis of the cortical axons' positions within CC and their projection pattern after crossing the midline showed that axon position within CC is critical for homotopic projection. Further genetic perturbations of semaphorin/neuropilin-1 signaling disrupted the axon order in CC, resulting in an ectopic contralateral axon projection that could not be corrected by developmental refinement.
Abstract
How developing axons in the corpus callosum (CC) achieve their homotopic projection to the contralateral cortex remains unclear. We found that axonal position within the CC plays a critical role in this projection. Labeling of nearby callosal axons in mice showed that callosal axons were segregated in an orderly fashion, with those from more medial cerebral cortex located more dorsally and subsequently projecting to more medial contralateral cortical regions. The normal axonal order within the CC was grossly disturbed when semaphorin3A/neuropilin-1 signaling was disrupted. However, the order in which axons were positioned within the CC still determined their contralateral projection, causing a severe disruption of the homotopic contralateral projection that persisted at postnatal day 30, when the normal developmental refinement of contralateral projections is completed in wild-type (WT) mice. Thus, the orderly positioning of axons within the CC is a primary determinant of how homotopic interhemispheric projections form in the contralateral cortex.
Footnotes
- ↵1To whom correspondence should be addressed. E-mail: mpoo{at}berkeley.edu.
Author contributions: J.Z., L.J.R., and M.-m.P. designed research; J.Z. performed research; J.Z., Y.W., L.S., Y.-n.S., and L.L. analyzed data; and J.Z., L.J.R., and M.-m.P. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1310233110/-/DCSupplemental.
Axon order determines the callosal projection
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- Biological Sciences
- Neuroscience
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