PDF(Pubmed)
Abstract：
Understanding the genetic programs that drive neuronal diversification into classes and subclasses is key to understand nervous system development. All neurons can be classified into two types: commissural and ipsilateral, based on whether their axons cross the midline or not. However, the gene regulatory program underlying this binary division is poorly understood. We identified a pair of basic helix-loop-helix transcription factors, Nhlh1 and Nhlh2, as a global transcriptional mechanism that controls the laterality of all floor plate-crossing commissural axons in mice. Mechanistically, Nhlh1/2 play an essential role in the expression of Robo3, the key guidance molecule for commissural axon projections. This genetic program appears to be evolutionarily conserved in chick. We further discovered that Isl1, primarily expressed in ipsilateral neurons within neural tubes, negatively regulates the Robo3 induction by Nhlh1/2. Our findings elucidate a gene regulatory strategy where a conserved global mechanism intersects with neuron class-specific regulators to control the partitioning of neurons based on axon laterality.
摘要：
了解驱动神经元多样化进入类和子类的遗传程序是了解神经系统发育的关键。所有神经元可分为两种类型：连合和同侧，基于它们的轴突是否越过中线。然而,这种二元划分背后的基因调控程序知之甚少。我们确定了一对基本的螺旋-环-螺旋转录因子，Nhlh1和Nhlh2，作为一种全局转录机制，控制小鼠所有底板交叉连合轴突的侧向性。机械上,Nhlh1/2在Robo3的表达中起重要作用，Robo3是连合轴突投射的关键指导分子。这种遗传程序在小鸡中似乎在进化上是保守的。我们进一步发现Isl1主要在神经管内的同侧神经元中表达，Nhlh1/2负调节Robo3诱导。我们的发现阐明了一种基因调控策略，其中保守的全局机制与神经元类特异性调节因子相交，以基于轴突侧向性来控制神经元的分区。
