Prdm12 represses the expression of the visceral neuron determinants Phox2a/b in developing somatosensory ganglia

Simon Vermeiren; Pauline Cabochette; Maya Dannawi; Simon Desiderio; Alba Sabaté San José; Younes Achouri; Sadia Kricha; Maren Sitte; Gabriela Salinas-Riester; Benoit Vanhollebeke; Jean-François Brunet; Eric J Bellefroid

doi:10.1016/j.isci.2023.108364

Prdm12 represses the expression of the visceral neuron determinants Phox2a/b in developing somatosensory ganglia

iScience. 2023 Oct 31;26(12):108364. doi: 10.1016/j.isci.2023.108364. eCollection 2023 Dec 15.

Affiliations

¹ Department of Molecular Biology, ULB Neuroscience Institute (UNI), Université libre de Bruxelles (ULB), B-6041 Gosselies, Belgium.
² Transgenesis Platform, de Duve Institute, Université Catholique de Louvain, Institut de Duve, Brussels, Belgium.
³ NGS Integrative Genomics, Department of Human Genetics at the University Medical Center Göttingen (UMG), 37075 Göttingen, Germany.
⁴ Institut de Biologie de l'ENS (IBENS), Inserm, CNRS, École Normale Supérieure, PSL Research University, 75005 Paris, France.
⁵ Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8197, 75005 Paris, France.
⁶ Institut National de la Santé et de la Recherche Médicale U1024, 75005 Paris, France.

Abstract

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.

Keywords: Biological sciences; Developmental neuroscience; Natural sciences; Neuroscience.