Temporal refinement of Dach1 expression contributes to the development of somatosensory neurons.

Tünde Szemes,Alba Sabaté San José,Abdulkader Azouz,Maren Sitte,Gabriela Salinas,Younes Achouri,Sadia Kricha,Laurence Ris,Kristy Red-Horse,Eric J Bellefroid,Simon Desiderio
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Abstract

During somatosensory neurogenesis, neurons are born in an unspecialized transcriptional state. Several transcription factors in these cells follow a broad-to-restricted expression trajectory as development proceeds, giving rise to neuron subtypes with different identities. The relevance of this temporal refinement of transcription factor expression remains unclear as the functions of transcription factors with broad-to-restricted expression patterns have been mostly studied in those neuron subtypes in which they remain active. Here we show that Dach1 encodes a bona fide transcription factor with a broad-to-restricted expression pattern retained and required in tactile somatosensory neurons. In developing nociceptors, Prdm12 contributes to Dach1 silencing. Using genetic approaches to prevent its temporal restriction during mouse somatosensory development, we reveal that Dach1 expression refinement is a prerequisite for the acquisition of an appropriate transcriptional profile in those somatosensory neuron subtypes in which it becomes ultimately silenced. These findings highlight the essential role played by Dach1 during somatosensory neuron development and demonstrate that the temporal pattern of broad-to-restricted expression followed by several transcription factors is physiologically important for the development of somatosensory neurons.
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Dach1表达的时间细化有助于体感觉神经元的发育。
在躯体感觉神经发生过程中,神经元出生时处于非特化转录状态。随着发育的进行,这些细胞中的一些转录因子遵循着从广泛表达到限制表达的轨迹,从而产生了具有不同特征的神经元亚型。转录因子表达的这种时间性细化的相关性仍不清楚,因为对具有从宽泛到受限表达模式的转录因子功能的研究大多集中在它们仍然活跃的神经元亚型中。在这里,我们发现 Dach1 编码了一种真正的转录因子,其表达模式从宽泛到受限,在触觉躯体感觉神经元中被保留和需要。在发育中的痛觉感受器中,Prdm12 有助于 Dach1 的沉默。我们利用遗传学方法阻止了小鼠躯体感觉发育过程中Dach1表达的时间限制,揭示了Dach1表达的细化是其在那些最终被沉默的躯体感觉神经元亚型中获得适当转录谱的先决条件。这些发现凸显了 Dach1 在躯体感觉神经元发育过程中所扮演的重要角色,并证明了几种转录因子从广泛表达到限制表达的时间模式对躯体感觉神经元的发育具有重要的生理意义。
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