Prdm12 is an essential regulator of nociceptive sensory neuron differentiation

Prdm12 is an essential regulator of nociceptive sensory neuron differentiation S. Desiderio1, S. Vermeiren1, C. Van Campenhout1, S. Kricha1, V. Nagy², K.A. Henningfeld³, J.M. Penninger², T. Pieler³, E.J. Bellefroid1.1 Laboratory of Developmental Genetics, Universite Libre de Bruxelles (ULB), ULB Neuroscience Institute, B-6041 Gosselies, Belgium² Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria³Department of Developmental Biochemistry, Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), University of Gottingen, 37077 Gottingen, GermanyPR homology domain-containing member 12 (PRDM12) belongs to a family of conserved transcription factors acting as epigenetic regulators of gene expression that are implicated in cell fate decisions and diseases. Prdm12 is an uncharacterized member of the family with restricted expression in the developing central and peripheral nervous system. We have previously shown that in the frog Prdm12 is critical for the differentiation of the specification of spinal cord V1 interneurons that are required for locomotion movements. Our past results have also indicated that Prdm12 is required in the frog for the expression of cranial sensory markers and that its overexpression in neuralized RA-treated animal cap explants is sufficient to induce their expression. These data together with the recent identification of mutations in Prdm12 in individuals with Congenital Insensitivity to Pain suggest that Prdm12 plays an important role in the development of nociceptive sensory neurons. We have investigated this possibility using knock-out mouse lines and gain of function experiments in the frog. The results obtain indicate that Prdm12 is essential for nociceptor development and suggest a role in mature nociceptors.