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

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

Sriram Sudarsanam1, Luis E Guzman-Clavel1, Nyle Dar1

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

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|April 14, 2025
PubMed
Summary
This summary is machine-generated.

The transcription factor Mef2c regulates neuronal identity in developing mouse brains. It also guides specific axon projections in postnatal callosal neurons by repressing EphA6 signaling.

Keywords:
Mef2caxon guidancecorpus callosumephrinsintracortical connectivityneocortex

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Genetics

Background:

  • Neuronal connectivity in the cerebral cortex is vital for information processing.
  • The precise development of neuronal classes and their axon projections is essential for cortical circuit formation.
  • Genetic factors governing intracortical axon targeting remain largely unknown.

Purpose of the Study:

  • To investigate the role of the transcription factor myocyte enhancer factor 2-c (Mef2c) in cortical development.
  • To identify the genetic determinants of intracortical axon targeting.
  • To elucidate the function of Mef2c in both embryonic and postnatal stages of neuronal development.

Main Methods:

  • Utilized murine models to study Mef2c's function during embryogenesis and postnatal development.
  • Examined Mef2c's role in specifying neuronal identity in somatosensory cortical (S1) layers.
  • Employed functional manipulation of EphrinA-EphA signaling in Mef2c mutant callosal projection neurons (CPNs).

Main Results:

  • Mef2c directs the development of S1 Layer 4 and 5 pyramidal neuron identity during embryogenesis.
  • Postnatal Mef2c expression shifts to Layer 2/3 CPNs, where it regulates axon targeting.
  • Mef2c represses EphA6 expression, desensitizing S1-L2/3 CPN axons to EphrinA5-mediated repulsion.

Conclusions:

  • Mef2c plays a dual role in cortical development.
  • It regulates laminar subtype specification in embryonic neurons.
  • It controls contralateral homotopic targeting of postnatal callosal projection axons.