Mef2c Controls Postnatal Callosal Axon Targeting by Regulating Sensitivity to Ephrin Repulsion

Overview

Journal bioRxiv

Date 2025 Feb 3

PMID 39896513

Authors

Sriram Sudarsanam

Luis Guzman-Clavel

Nyle Dar

Jakub Ziak

Naseer Shahid

Xinyu O Jin

Alex L Kolodkin

Affiliations

Soon will be listed here.

Abstract

Cortical connectivity is contingent on ordered emergence of neuron subtypes followed by the formation of subtype-specific axon projections. Intracortical circuits, including long-range callosal projections, are crucial for information processing, but mechanisms of intracortical axon targeting are still unclear. We find that the transcription factor Myocyte enhancer factor 2-c (Mef2c) directs the development of somatosensory cortical (S1) layer 4 and 5 pyramidal neurons during embryogenesis. During early postnatal development, expression shifts to layer 2/3 callosal projection neurons (L2/3 CPNs), and we find a novel function for in targeting homotopic contralateral cortical regions by S1-L2/3 CPNs. We demonstrate, using functional manipulation of EphA-EphrinA signaling in mutant CPNs, that Mef2c downregulates 6 to desensitize S1-L2/3 CPN axons to EphrinA5-repulsion at their contralateral targets. Our work uncovers dual roles for in cortical development: regulation of laminar subtype specification during embryogenesis, and axon targeting in postnatal callosal neurons.

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