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

Sriram Sudarsanam1,2, Luis Guzman-Clavel1,2, Nyle Dar1

  • 1The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins Kavli Neuroscience Discovery Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

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|February 3, 2025
PubMed
Summary
This summary is machine-generated.

The transcription factor Mef2c regulates neuron development and axon targeting in the cerebral cortex. It controls subtype specification and guides callosal projection neurons to their correct targets.

Keywords:
EphrinsIntracortical connectivityMef2caxon guidancecorpus callosumneocortex

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Molecular Biology

Background:

  • Cortical connectivity relies on precise neuron subtype development and axon projection.
  • Mechanisms governing intracortical axon targeting, especially for callosal projections, remain incompletely understood.

Purpose of the Study:

  • To investigate the role of the transcription factor Myocyte enhancer factor 2-c (Mef2c) in cortical development.
  • To elucidate Mef2c's function in the specification of somatosensory cortical (S1) neurons and the targeting of layer 2/3 callosal projection neurons (L2/3 CPNs).

Main Methods:

  • Utilized genetic manipulation to study Mef2c function in developing cortical neurons.
  • Investigated the interplay between Mef2c and EphA-EphrinA signaling pathways.
  • Analyzed axon targeting of L2/3 CPNs in Mef2c-mutant models.

Main Results:

  • Mef2c directs the development of S1 layer 4 and 5 pyramidal neurons during embryogenesis.
  • Postnatally, Mef2c expression shifts to L2/3 CPNs, where it mediates targeting to homotopic contralateral cortical regions.
  • Mef2c downregulates EphA6 expression, desensitizing S1-L2/3 CPN axons to EphrinA5-mediated repulsion.

Conclusions:

  • Mef2c exhibits dual roles in cortical development: regulating neuronal subtype specification and directing postnatal callosal axon targeting.
  • This study reveals a novel mechanism for Mef2c in guiding long-range axon projections via modulation of Ephrin signaling.