Centre for Integrative Physiology, School of Biomedical Sciences, University of Edinburgh, Edinburgh, United Kingdom.
PLoS Biol. 2011 Jan 4;9(1):e1000568. doi: 10.1371/journal.pbio.1000568.
In neurogenesis, neural cell fate specification is generally triggered by proneural transcription factors. Whilst the role of proneural factors in fate specification is well studied, the link between neural specification and the cellular pathways that ultimately must be activated to construct specialised neurons is usually obscure. High-resolution temporal profiling of gene expression reveals the events downstream of atonal proneural gene function during the development of Drosophila chordotonal (mechanosensory) neurons. Among other findings, this reveals the onset of expression of genes required for construction of the ciliary dendrite, a key specialisation of mechanosensory neurons. We determine that atonal activates this cellular differentiation pathway in several ways. Firstly, atonal directly regulates Rfx, a well-known highly conserved ciliogenesis transcriptional regulator. Unexpectedly, differences in Rfx regulation by proneural factors may underlie variations in ciliary dendrite specialisation in different sensory neuronal lineages. In contrast, fd3F encodes a novel forkhead family transcription factor that is exclusively expressed in differentiating chordotonal neurons. fd3F regulates genes required for specialized aspects of chordotonal dendrite physiology. In addition to these intermediate transcriptional regulators, we show that atonal directly regulates a novel gene, dilatory, that is directly associated with ciliogenesis during neuronal differentiation. Our analysis demonstrates how early cell fate specification factors can regulate structural and physiological differentiation of neuronal cell types. It also suggests a model for how subtype differentiation in different neuronal lineages may be regulated by different proneural factors. In addition, it provides a paradigm for how transcriptional regulation may modulate the ciliogenesis pathway to give rise to structurally and functionally specialised ciliary dendrites.
在神经发生中，神经细胞命运的特化通常是由神经前转录因子触发的。虽然神经前因子在命运特化中的作用已经得到了很好的研究，但神经特化与最终必须激活的细胞途径之间的联系通常是不清楚的。高分辨率的基因表达时程分析揭示了果蝇琴形（机械感觉）神经元发育过程中 atonal 神经前基因功能下游的事件。除其他发现外，这揭示了构建纤毛树突所必需的基因的表达开始，这是机械感觉神经元的一个关键特化。我们确定 atonal 以几种方式激活了这个细胞分化途径。首先，atonal 直接调节 Rfx，这是一个众所周知的高度保守的纤毛发生转录调节因子。出乎意料的是，神经前因子对 Rfx 的调节差异可能是不同感觉神经元谱系中纤毛树突特化的差异的基础。相比之下，fd3F 编码一种新型的 forkhead 家族转录因子，它只在分化的琴形神经元中表达。fd3F 调节专门的琴形神经元树突生理学所必需的基因。除了这些中间转录调节因子，我们还表明 atonal 直接调节一个新的基因 dilatory，它在神经元分化过程中与纤毛发生直接相关。我们的分析表明了早期的细胞命运特化因子如何调节神经元细胞类型的结构和生理分化。它还提出了一个模型，说明不同的神经前因子如何调节不同神经元谱系中的亚型分化。此外，它为转录调节如何调节纤毛发生途径以产生结构和功能特化的纤毛树突提供了一个范例。
