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Conditional Dnmt1 deletion in dorsal forebrain disrupts development of somatosensory barrel cortex and thalamocortical long-term potentiation

Published online by Cambridge University Press:  05 March 2007

Peyman Golshani
Affiliation:
Dept of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, USA
Leah Hutnick
Affiliation:
Neuroscience Interdepartmental Program, David Geffen School of Medicine, UCLA, Los Angeles, USA
Felix Schweizer
Affiliation:
Dept of Neurobiology, David Geffen School of Medicine, UCLA, Los Angeles, USA
Guoping Fan
Affiliation:
Dept of Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, USA

Abstract

The transcriptional mechanisms that govern the development and plasticity of somatopic sensory maps in the cerebral cortex have not been studied extensively. In particular, no studies have addressed the role of epigenetic mechanisms in the development of sensory maps. DNA methylation is one of the main epigenetic mechanisms by which mammalian cells regulate gene transcription. Demethylation results in embryonic lethality, so it has been very difficult to study the role of DNA methylation in brain development. We have used cre-loxP technology to generate forebrain-specific deletion of DNA methyltransferase 1 (Dnmt1), the enzyme required for the maintenance of DNA methylation. We find that DNA hypomethylation of neurons in the cerebral cortex results in the failure of development of somatosensory barrel cortex. We also find that, despite functional thalamocortical neurotransmission, thalamocortical long-term potentiation cannot be induced in slices from Emx1-cre;Dnmt1 mutant mice. These studies emphasize the importance of DNA methylation for the development of sensory maps and indicate that epigenetic mechanisms might play a role in the development of synaptic plasticity.

Type
Research Article
Copyright
2007 Cambridge University Press

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