Department of Life Sciences, Imperial College London, Sir Ernst Chain Building, London SW7 2AZ, UK.
Department of Life Sciences, Imperial College London, Sir Ernst Chain Building, London SW7 2AZ, UK
Biol Open. 2020 Jun 3;9(5):bio052928. doi: 10.1242/bio.052928.
The remarkable diversity of neurons in the nervous system is generated during development, when properties such as cell morphology, receptor profiles and neurotransmitter identities are specified. In order to gain a greater understanding of neurotransmitter specification we profiled the transcription state of cholinergic, GABAergic and glutamatergic neurons at three developmental time points. We identified 86 differentially expressed transcription factors that are uniquely enriched, or uniquely depleted, in a specific neurotransmitter type. Some transcription factors show a similar profile across development, others only show enrichment or depletion at specific developmental stages. Profiling of Acj6 (cholinergic enriched) and Ets65A (cholinergic depleted) binding sites reveals that they both directly bind the locus, in addition to a wide spectrum of other key neuronal differentiation genes. We also show that cholinergic enriched transcription factors are expressed in mostly non-overlapping populations in the adult brain, implying the absence of combinatorial regulation of neurotransmitter fate in this context. Furthermore, our data underlines that, similar to , there are no simple transcription factor codes for neurotransmitter type specification.This article has an associated First Person interview with the first author of the paper.
神经系统中神经元的显著多样性是在发育过程中产生的，在此期间，细胞形态、受体谱和神经递质特性等特性被确定。为了更深入地了解神经递质的特异性，我们在三个发育时间点对胆碱能、GABA 能和谷氨酸能神经元的转录状态进行了分析。我们鉴定了 86 个差异表达的转录因子，它们在特定的神经递质类型中特异性富集或耗尽。一些转录因子在整个发育过程中表现出相似的特征，而另一些转录因子仅在特定的发育阶段表现出富集或耗尽。Acj6（胆碱能富集）和 Ets65A（胆碱能耗尽）结合位点的分析表明，它们都直接结合了 基因座，此外还结合了广泛的其他关键神经元分化基因。我们还表明，胆碱能富集的转录因子在成年大脑中的表达群体大多不重叠，这意味着在这种情况下，神经递质命运的组合调控不存在。此外，我们的数据强调，与 类似，神经递质类型特异性的转录因子没有简单的编码。本文附有该论文第一作者的第一人称采访。
