Department of Biology, New York University, New York, NY 10003, USA.
Flatiron Institute, Center for Computational Biology, Simons Foundation, New York, NY 10010, USA.
Science. 2022 Dec 23;378(6626):eadd1884. doi: 10.1126/science.add1884.
The large diversity of cell types in nervous systems presents a challenge in identifying the genetic mechanisms that encode it. Here, we report that nearly 200 distinct neurons in the visual system can each be defined by unique combinations of on average 10 continuously expressed transcription factors. We show that targeted modifications of this terminal selector code induce predictable conversions of neuronal fates that appear morphologically and transcriptionally complete. Cis-regulatory analysis of open chromatin links one of these genes to an upstream patterning factor that specifies neuronal fates in stem cells. Experimentally validated network models describe the synergistic regulation of downstream effectors by terminal selectors and ecdysone signaling during brain wiring. Our results provide a generalizable framework of how specific fates are implemented in postmitotic neurons.
神经系统中细胞类型的多样性很大，这给确定编码它的遗传机制带来了挑战。在这里，我们报告说，视觉系统中的近 200 种不同的神经元可以通过平均 10 种连续表达的转录因子的独特组合来定义。我们表明，这种终末选择器代码的靶向修饰会诱导神经元命运的可预测转换，这些转换在形态和转录上都是完整的。开放染色质的顺式调控分析将其中一个基因与一个上游模式形成因子联系起来，该因子在干细胞中指定神经元命运。经过实验验证的网络模型描述了终末选择器和蜕皮激素信号在大脑布线过程中对下游效应物的协同调节。我们的研究结果提供了一个可推广的框架，说明了特定命运是如何在有丝分裂后神经元中实现的。
