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Curr Biol. 2018 Jun 4;28(11):1768-1782.e4. doi: 10.1016/j.cub.2018.04.026. Epub 2018 May 17.

Developmental Upregulation of Ephrin-B1 Silences Sema3C/Neuropilin-1 Signaling during Post-crossing Navigation of Corpus Callosum Axons.

Author information

1
Aix Marseille Univ, CNRS, IBDM, 13288 Marseille, France. Electronic address: mire.erik@gmail.com.
2
Aix Marseille Univ, CNRS, IBDM, 13288 Marseille, France.
3
Centre de Biologie du Développement (CBD), Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, 118 Route de Narbonne, 31062 Toulouse, France.
4
Aix Marseille Univ, CNRS, IBDM, 13288 Marseille, France. Electronic address: fanny.mann@univ-amu.fr.

Abstract

The corpus callosum is the largest commissure in the brain, whose main function is to ensure communication between homotopic regions of the cerebral cortex. During fetal development, corpus callosum axons (CCAs) grow toward and across the brain midline and then away on the contralateral hemisphere to their targets. A particular feature of this circuit, which raises a key developmental question, is that the outgoing trajectory of post-crossing CCAs is mirror-symmetric with the incoming trajectory of pre-crossing axons. Here, we show that post-crossing CCAs switch off their response to axon guidance cues, among which the secreted Semaphorin-3C (Sema3C), that act as attractants for pre-crossing axons on their way to the midline. This change is concomitant with an upregulation of the surface protein Ephrin-B1, which acts in CCAs to inhibit Sema3C signaling via interaction with the Neuropilin-1 (Nrp1) receptor. This silencing activity is independent of Eph receptors and involves a N-glycosylation site (N-139) in the extracellular domain of Ephrin-B1. Together, our results reveal a molecular mechanism, involving interaction between the two unrelated guidance receptors Ephrin-B1 and Nrp1, that is used to control the navigation of post-crossing axons in the corpus callosum.

KEYWORDS:

axon guidance; corpus callosum; cortex; ephrins; neuropilins; semaphorins

PMID:
29779877
DOI:
10.1016/j.cub.2018.04.026

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