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Updated: May 23, 2025
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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.
Summary
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.
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.
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