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PRDM12 Is Required for Initiation of the Nociceptive Neuron Lineage during Neurogenesis.
Cell Reports ( IF 7.5 ) Pub Date : 2019-03-26 , DOI: 10.1016/j.celrep.2019.02.098 Luca Bartesaghi 1 , Yiqiao Wang 2 , Paula Fontanet 2 , Simone Wanderoy 2 , Finja Berger 1 , Haohao Wu 2 , Natalia Akkuratova 3 , Filipa Bouçanova 1 , Jean-Jacques Médard 1 , Charles Petitpré 2 , Mark A Landy 4 , Ming-Dong Zhang 5 , Philip Harrer 6 , Claudia Stendel 6 , Rolf Stucka 6 , Marina Dusl 6 , Maria Eleni Kastriti 7 , Laura Croci 8 , Helen C Lai 4 , Gian Giacomo Consalez 9 , Alexandre Pattyn 10 , Patrik Ernfors 5 , Jan Senderek 6 , Igor Adameyko 7 , Francois Lallemend 2 , Saida Hadjab 2 , Roman Chrast 1
Cell Reports ( IF 7.5 ) Pub Date : 2019-03-26 , DOI: 10.1016/j.celrep.2019.02.098 Luca Bartesaghi 1 , Yiqiao Wang 2 , Paula Fontanet 2 , Simone Wanderoy 2 , Finja Berger 1 , Haohao Wu 2 , Natalia Akkuratova 3 , Filipa Bouçanova 1 , Jean-Jacques Médard 1 , Charles Petitpré 2 , Mark A Landy 4 , Ming-Dong Zhang 5 , Philip Harrer 6 , Claudia Stendel 6 , Rolf Stucka 6 , Marina Dusl 6 , Maria Eleni Kastriti 7 , Laura Croci 8 , Helen C Lai 4 , Gian Giacomo Consalez 9 , Alexandre Pattyn 10 , Patrik Ernfors 5 , Jan Senderek 6 , Igor Adameyko 7 , Francois Lallemend 2 , Saida Hadjab 2 , Roman Chrast 1
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The sensation of pain is essential for the preservation of the functional integrity of the body. However, the key molecular regulators necessary for the initiation of the development of pain-sensing neurons have remained largely unknown. Here, we report that, in mice, inactivation of the transcriptional regulator PRDM12, which is essential for pain perception in humans, results in a complete absence of the nociceptive lineage, while proprioceptive and touch-sensitive neurons remain. Mechanistically, our data reveal that PRDM12 is required for initiation of neurogenesis and activation of a cascade of downstream pro-neuronal transcription factors, including NEUROD1, BRN3A, and ISL1, in the nociceptive lineage while it represses alternative fates other than nociceptors in progenitor cells. Our results thus demonstrate that PRDM12 is necessary for the generation of the entire lineage of pain-initiating neurons.
中文翻译：
在神经发生过程中，伤害性神经元谱系的启动需要PRDM12。
疼痛感对于维持身体的功能完整性至关重要。然而，对于痛觉神经元的发育开始所必需的关键分子调节剂仍是未知的。在这里，我们报告说，在小鼠中，转录调节剂PRDM12的失活对人类的疼痛感知至关重要，导致完全没有伤害感受谱系，而本体感受和触敏神经元仍然存在。从机理上讲，我们的数据显示PRDM12是伤害性谱系启动神经发生和激活级联下游神经元转录因子（包括NEUROD1，BRN3A和ISL1）所必需的，同时它抑制了祖细胞中伤害性感受器以外的其他命运。
更新日期：2019-03-27
中文翻译：
在神经发生过程中，伤害性神经元谱系的启动需要PRDM12。
疼痛感对于维持身体的功能完整性至关重要。然而，对于痛觉神经元的发育开始所必需的关键分子调节剂仍是未知的。在这里，我们报告说，在小鼠中，转录调节剂PRDM12的失活对人类的疼痛感知至关重要，导致完全没有伤害感受谱系，而本体感受和触敏神经元仍然存在。从机理上讲，我们的数据显示PRDM12是伤害性谱系启动神经发生和激活级联下游神经元转录因子（包括NEUROD1，BRN3A和ISL1）所必需的，同时它抑制了祖细胞中伤害性感受器以外的其他命运。
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