Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA; Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
Neuron. 2020 Sep 9;107(5):874-890.e8. doi: 10.1016/j.neuron.2020.06.008. Epub 2020 Jun 25.
The maturation of the mammalian brain occurs after birth, and this stage of neuronal development is frequently impaired in neurological disorders, such as autism and schizophrenia. However, the mechanisms that regulate postnatal brain maturation are poorly defined. By purifying neuronal subpopulations across brain development in mice, we identify a postnatal switch in the transcriptional regulatory circuits that operates in the maturing mammalian brain. We show that this developmental transition includes the formation of hundreds of cell-type-specific neuronal enhancers that appear to be modulated by neuronal activity. Once selected, these enhancers are active throughout adulthood, suggesting that their formation in early life shapes neuronal identity and regulates mature brain function.
哺乳动物大脑的成熟发生在出生后，而神经元发育的这一阶段在自闭症和精神分裂症等神经疾病中经常受到损害。然而，调节产后大脑成熟的机制还没有被很好地定义。通过在小鼠的大脑发育过程中纯化神经元亚群，我们确定了在成熟的哺乳动物大脑中起作用的转录调控回路的产后开关。我们表明，这种发育转变包括数百种细胞类型特异性神经元增强子的形成，这些增强子似乎受到神经元活动的调节。一旦被选择，这些增强子在整个成年期都保持活跃，这表明它们在生命早期的形成塑造了神经元的身份，并调节了成熟大脑的功能。
