Department of Neurosciences, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USA.
Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, Howard Hughes Medical Institute, New York, New York, USA.
Nat Neurosci. 2014 Jul;17(7):899-907. doi: 10.1038/nn.3731. Epub 2014 Jun 15.
The identity of specific cell types in the nervous system is defined by the expression of neuron type-specific gene batteries. How the expression of such batteries is initiated during nervous system development has been under intensive study over the past few decades. However, comparatively little is known about how gene batteries that define the terminally differentiated state of a neuron type are maintained throughout the life of an animal. Here we provide an overview of studies in invertebrate and vertebrate model systems that have carved out the general and not commonly appreciated principle that neuronal identity is maintained in postmitotic neurons by the sustained, and often autoregulated, expression of the same transcription factors that initiate terminal differentiation in a developing organism. Disruption of postmitotic maintenance mechanisms may result in neuropsychiatric and neurodegenerative conditions.
神经系统中特定细胞类型的身份由神经元类型特异性基因电池的表达来定义。在过去的几十年中,人们一直在深入研究这些基因电池在神经系统发育过程中是如何被启动的。然而,对于定义神经元类型终末分化状态的基因电池是如何在动物的整个生命周期中维持的,我们知之甚少。在这里,我们提供了一个在无脊椎动物和脊椎动物模型系统中的研究综述,这些研究揭示了一个普遍但尚未被广泛认识的原则,即神经元的身份是通过在发育中的生物体中启动终末分化的相同转录因子的持续表达来维持的,而且这种表达通常是自我调节的。破坏有丝后维持机制可能导致神经精神和神经退行性疾病。