PR homology domain-containing member 12 (PRDM12) belongs to a family of 
conserved transcription factors implicated in cell fate decisions. Here we show 
that PRDM12 is a key regulator of sensory neuronal specification in Xenopus. 
Modeling of human PRDM12 mutations that cause hereditary sensory and autonomic 
neuropathy (HSAN) revealed remarkable conservation of the mutated residues in 
evolution. Expression of wild-type human PRDM12 in Xenopus induced the 
expression of sensory neuronal markers, which was reduced using various human 
PRDM12 mutants. In Drosophila, we identified Hamlet as the functional PRDM12 
homolog that controls nociceptive behavior in sensory neurons. Furthermore, 
expression analysis of human patient fibroblasts with PRDM12 mutations uncovered 
possible downstream target genes. Knockdown of several of these target genes 
including thyrotropin-releasing hormone degrading enzyme (TRHDE) in Drosophila 
sensory neurons resulted in altered cellular morphology and impaired 
nociception. These data show that PRDM12 and its functional fly homolog Hamlet 
are evolutionary conserved master regulators of sensory neuronal specification 
and play a critical role in pain perception. Our data also uncover novel 
pathways in multiple species that regulate evolutionary conserved nociception.