Szemes Tünde, Sabaté San José Alba, Azouz Abdulkader, Sitte Maren, Salinas Gabriela, Achouri Younes, Kricha Sadia, Ris Laurence, Red-Horse Kristy, Bellefroid Eric J, Desiderio Simon
Department of Molecular Biology, ULB Neuroscience Institute (UNI), Université Libre de Bruxelles (ULB), Gosselies, Belgium.
Laboratory of Neuroscience, UMONS Research Institute for Health Sciences and Technology, University of Mons, Mons, Belgium.
EMBO J. 2025 May;44(10):2882-2905. doi: 10.1038/s44318-025-00427-y. Epub 2025 Apr 9.
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.
在躯体感觉神经发生过程中,神经元以未特化的转录状态产生。随着发育的进行,这些细胞中的几种转录因子遵循从广泛表达到受限表达的轨迹,产生具有不同身份的神经元亚型。由于具有广泛到受限表达模式的转录因子的功能大多是在它们保持活跃的那些神经元亚型中进行研究的,这种转录因子表达的时间精细化的相关性仍不清楚。在这里,我们表明Dach1编码一种真正的转录因子,其具有在触觉躯体感觉神经元中保留并必需的从广泛表达到受限表达的模式。在发育中的伤害感受器中,Prdm12导致Dach1沉默。利用基因方法在小鼠躯体感觉发育过程中防止其时间限制,我们发现Dach1表达的精细化是在那些最终沉默它的躯体感觉神经元亚型中获得适当转录谱的先决条件。这些发现突出了Dach1在躯体感觉神经元发育过程中所起的重要作用,并证明了几种转录因子遵循的从广泛到受限表达的时间模式对躯体感觉神经元的发育在生理上是重要的。