The gene regulatory cascade linking proneural specification with differentiation in Drosophila sensory neurons.
The gene regulatory cascade linking proneural specification with differentiation in Drosophila sensory neurons.
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DOI：
10.1371/journal.pbio.1000568
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发表时间：
2011-01-04
期刊：
影响因子：
9.8
通讯作者：
Jarman AP
中科院分区：
文献类型：
--
作者：
Cachero S;Simpson TI;Zur Lage PI;Ma L;Newton FG;Holohan EE;Armstrong JD;Jarman AP
感觉前体细胞的时间表达谱揭示了无调前神经转录因子如何调节专门的神经元分化途径。在神经发生中，神经细胞命运特化通常由前神经转录因子触发。虽然前神经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被激活以构建专门神经元的细胞通路之间的联系通常是模糊的。基因表达的高分辨率时间分析揭示了果蝇弦音（机械感觉）神经元发育过程中无调前神经基因功能下游的事件。在其他研究结果中，这揭示了纤毛树突（机械感觉神经元的关键特化）构建所需基因表达的开始。我们确定，无调激活这种细胞分化途径在几个方面。首先，无调直接调节Rfx，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，在Rfx调节的前神经因素的差异可能是在不同的感觉神经元谱系的睫状树突专门化的变化。相比之下，fd3F编码一种新的叉头家族转录因子，该因子仅在分化的弦音神经元中表达。fd3F调节弦音树突生理学的专门方面所需的基因。除了这些中间转录调节因子，我们表明，无调直接调节一种新的基因，dilatory，这是直接与神经元分化过程中的纤毛发生。我们的分析表明，早期细胞命运规范因子可以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，在不同的神经元谱系亚型分化可能受到不同的前神经因子。此外，它提供了一个范例，转录调控如何可能调节纤毛发生途径，产生结构和功能专门的纤毛树突。在发育的早期，细胞分化并具有专门的形式和功能。这需要激活不同细胞途径的特定基因。我们的研究解决了这种激活是如何在发育中的果蝇神经系统的调节。在该模型中，众所周知，前神经转录因子参与指导细胞分化成各种类型的神经元。然而，他们设计神经元分化基因激活的机制尚不清楚。在这项研究中，我们专注于导致机械感觉神经元分化的事件，这些神经元具有介导感觉感知的专门树突过程。在这些发育中的神经元中，我们描绘了由前神经因子无调触发的基因表达的时间过程。我们的分析揭示了形成这些特殊树突（称为纤毛）所需的基因的激活。然后，我们确定了几种方式，无调调节这些基因。首先，它激活调节分化基因不同子集的中间转录因子。第二，至少在一种情况下，无调性直接激活分化基因，一个参与纤毛形成（纤毛发生）的基因。这些发现为前神经因子如何调节专门的神经元分化途径提供了新的见解。
Temporal expression profiling of sensory precursor cells reveals how the atonal proneural transcription factor regulates a specialized neuronal differentiation pathway. 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. Early during development, cells differentiate and take on specialized forms and functions. This requires the activation of specific genes for different cellular pathways. Our study addresses how this activation is regulated in the developing Drosophila nervous system. In this model, it is well known that proneural transcription factors are involved in directing cells to differentiate into various types of neurons. However, the mechanism by which they choreograph the activation of genes for neuronal differentiation is not clear. In this study, we focused on events leading to differentiation of mechanosensory neurons, which have specialized dendritic processes that mediate sensory perception. In these developing neurons we profiled the time course of gene expression that is triggered by the proneural factor atonal. Our analysis revealed the activation of genes required for the formation of these specialized dendrites, called cilia. We then identified several ways in which atonal regulated these genes. First, it activates intermediate transcription factors that regulate different subsets of differentiation genes. Second, in at least one case, atonal activates a differentiation gene directly, one that is involved in the formation of cilia (ciliogenesis). These findings offer new insight into how proneural factors regulate specialized neuronal differentiation pathways.
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影响因子：
14.9
作者：
Hubbard, T;Barker, D;Clamp, M
通讯作者：
Clamp, M
影响因子：
10.5
作者：
BLOCHLINGER, K;JAN, LY;JAN, YN
通讯作者：
JAN, YN
影响因子：
2.7
作者：
Goulding, SE;White, NM;Jarman, AP
通讯作者：
Jarman, AP
影响因子：
64.5
作者：
Gerdes JM;Davis EE;Katsanis N
通讯作者：
Katsanis N
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y