Kerk Sze Yen, Kratsios Paschalis, Hart Michael, Mourao Romulo, Hobert Oliver
Department of Biological Sciences, Howard Hughes Medical Institute, Columbia University, New York, NY 10027, USA.
Department of Biological Sciences, Howard Hughes Medical Institute, Columbia University, New York, NY 10027, USA.
Neuron. 2017 Jan 4;93(1):80-98. doi: 10.1016/j.neuron.2016.11.036.
A common organizational feature of nervous systems is the existence of groups of neurons that share common traits but can be divided into individual subtypes based on anatomical or molecular features. We elucidate the mechanistic basis of neuronal diversification processes in the context of C.elegans ventral cord motor neurons that share common traits that are directly activated by the terminal selector UNC-3. Diversification of motor neurons into different classes, each characterized by unique patterns of effector gene expression, is controlled by distinct combinations of phylogenetically conserved, class-specific transcriptional repressors. These repressors are continuously required in postmitotic neurons to prevent UNC-3, which is active in all neuron classes, from activating class-specific effector genes in specific motor neuron subsets via discrete cis-regulatory elements. The strategy of antagonizing the activity of broadly acting terminal selectors of neuron identity in a subtype-specific fashion may constitute a general principle of neuron subtype diversification.
神经系统的一个常见组织特征是存在一组具有共同特征的神经元,但可根据解剖学或分子特征分为不同的亚型。我们在秀丽隐杆线虫腹侧神经索运动神经元的背景下阐明了神经元多样化过程的机制基础,这些运动神经元具有共同特征,可被终端选择因子UNC-3直接激活。运动神经元分化为不同类别,每个类别具有独特的效应基因表达模式,这是由系统发育保守的、类别特异性转录抑制因子的不同组合控制的。在有丝分裂后神经元中持续需要这些抑制因子,以防止在所有神经元类别中都活跃的UNC-3通过离散的顺式调控元件在特定运动神经元亚群中激活类别特异性效应基因。以亚型特异性方式拮抗广泛作用的神经元身份终端选择因子活性的策略可能构成神经元亚型多样化的一般原则。