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Prdm12 represses the expression of the visceral neuron determinants Phox2a/b in developing somatosensory ganglia
iScience ( IF 4.6 ) Pub Date : 2023-10-31 , DOI: 10.1016/j.isci.2023.108364 Simon Vermeiren 1 , Pauline Cabochette 1 , Maya Dannawi 1 , Simon Desiderio 1 , Alba Sabaté San José 1 , Younes Achouri 2 , Sadia Kricha 1 , Maren Sitte 3 , Gabriela Salinas-Riester 3 , Benoit Vanhollebeke 1 , Jean-François Brunet 4, 5, 6 , Eric J Bellefroid 1
iScience ( IF 4.6 ) Pub Date : 2023-10-31 , DOI: 10.1016/j.isci.2023.108364 Simon Vermeiren 1 , Pauline Cabochette 1 , Maya Dannawi 1 , Simon Desiderio 1 , Alba Sabaté San José 1 , Younes Achouri 2 , Sadia Kricha 1 , Maren Sitte 3 , Gabriela Salinas-Riester 3 , Benoit Vanhollebeke 1 , Jean-François Brunet 4, 5, 6 , Eric J Bellefroid 1
Affiliation
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Prdm12 is a transcriptional regulator essential for the emergence of the somatic nociceptive lineage during sensory neurogenesis. The exact mechanisms by which Prdm12 promotes nociceptor development remain, however, poorly understood. Here, we report that the trigeminal and dorsal root ganglia hypoplasia induced by the loss of Prdm12 involves Bax-dependent apoptosis and that it is accompanied by the ectopic expression of the visceral sensory neuron determinants Phox2a and Phox2b , which is, however, not sufficient to impose a complete fate switch in surviving somatosensory neurons. Mechanistically, our data reveal that Prdm12 is required from somatosensory neural precursors to early post-mitotic differentiating nociceptive neurons to repress Phox2a/b and that its repressive function is context dependent. Together, these findings reveal that besides its essential role in nociceptor survival during development, Prdm12 also promotes nociceptor fate via an additional mechanism, by preventing precursors from engaging into an alternate Phox2 driven visceral neuronal type differentiation program.
中文翻译：
Prdm12 在发育中的体感神经节中抑制内脏神经元决定因素 Phox2a/b 的表达
Prdm12 是一种转录调节因子，对于感觉神经发生过程中体细胞伤害性谱系的出现至关重要。然而，Prdm12 促进伤害感受器发育的确切机制仍然知之甚少。在这里，我们报道了由 Prdm12 丢失诱导的三叉神经根神经节发育不全涉及 Bax 依赖性细胞凋亡，并且它伴随着内脏感觉神经元决定因素 Phox2a 和 Phox2b 的异位表达，然而，这不足以在幸存的体感神经元中施加完全的命运转换。从机制上讲，我们的数据显示 Prdm12 需要从体感神经前体到有丝分裂后早期分化伤害感受神经元来抑制 Phox2a/b，并且其抑制功能取决于环境。总之，这些发现揭示了除了在发育过程中伤害感受器存活中的重要作用外，Prdm12 还通过一种额外的机制促进伤害感受器的命运，通过阻止前体参与替代的 Phox2 驱动的内脏神经元类型分化程序。
更新日期：2023-10-31
中文翻译：
Prdm12 在发育中的体感神经节中抑制内脏神经元决定因素 Phox2a/b 的表达
Prdm12 是一种转录调节因子，对于感觉神经发生过程中体细胞伤害性谱系的出现至关重要。然而，Prdm12 促进伤害感受器发育的确切机制仍然知之甚少。在这里，我们报道了由 Prdm12 丢失诱导的三叉神经根神经节发育不全涉及 Bax 依赖性细胞凋亡，并且它伴随着内脏感觉神经元决定因素 Phox2a 和 Phox2b 的异位表达，然而，这不足以在幸存的体感神经元中施加完全的命运转换。从机制上讲，我们的数据显示 Prdm12 需要从体感神经前体到有丝分裂后早期分化伤害感受神经元来抑制 Phox2a/b，并且其抑制功能取决于环境。总之，这些发现揭示了除了在发育过程中伤害感受器存活中的重要作用外，Prdm12 还通过一种额外的机制促进伤害感受器的命运，通过阻止前体参与替代的 Phox2 驱动的内脏神经元类型分化程序。
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