Golshani Peyman, Hutnick Leah, Schweizer Felix, Fan Guoping
Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095.
Thalamus Relat Syst. 2005 Sep;3(3):227-233. doi: 10.1017/S1472928807000222.
The transcriptional mechanisms governing the development and plasticity of somatopic sensory maps in the cerebral cortex have not been extensively studied. In particular, no studies have addressed the role of epigenetic mechanisms in the development of sensory maps. DNA methylation is one the main epigenetic mechanisms available to mammalian cells to regulate gene transcription. As demethylation results in embryonic lethality, it has been very difficult to study the role of DNA methylation in brain development. We have used cre-lox technology to generate forebrain-specific deletion of DNA methyltransferase 1 (Dnmt1), the enzyme required for the maintenance of DNA methylation. We find that demethylation of neurons in the cerebral cortex results in the failure of development of somatosensory barrel cortex. We also find that in spite of functional thalamocortical neurotransmission, thalamocortical long-term potentiation cannot be induced in slices from Dnmt1 conditional mutants. These studies emphasize the importance of DNA methylation for the development of sensory maps and suggest epigenetic mechanisms may play a role in the development of synaptic plasticity.
大脑皮质躯体感觉图谱发育和可塑性的转录机制尚未得到广泛研究。特别是，尚无研究探讨表观遗传机制在感觉图谱发育中的作用。DNA甲基化是哺乳动物细胞可用于调节基因转录的主要表观遗传机制之一。由于去甲基化会导致胚胎致死，因此很难研究DNA甲基化在大脑发育中的作用。我们利用cre-lox技术在前脑特异性缺失维持DNA甲基化所需的酶——DNA甲基转移酶1（Dnmt1）。我们发现大脑皮质神经元的去甲基化会导致躯体感觉桶状皮质发育失败。我们还发现，尽管存在功能性丘脑皮质神经传递，但在Dnmt1条件性突变体的切片中无法诱导丘脑皮质长时程增强。这些研究强调了DNA甲基化对感觉图谱发育的重要性，并表明表观遗传机制可能在突触可塑性的发育中发挥作用。
