Pea3 transcription factors as mediators of nociception

DE VINCENTI AP; PARATCHA G; BRUMOVSKY P; LEDDA F; RÍOS AS; AQUINO J

Córdoba

Congreso; XXXIII Congreso Anual de la Sociedad Argentina de Neurociencias; 2018

Sociedad Argentina de Neurociencias

Sensory neurons of the dorsal root ganglion(DRG) are involved in the correct perception of external stimuli and requires the appropriate peripheral target tissue innervation. The majority of DRG neurons, have a small-diameter soma, express the neurotrophin receptor TrkA during embryonic development, and project unmyelinated fibers to innervate the epidermis, depending on target-derived nerve growth factor (NGF). In mammals, peripheral neurotrophic signals have been shown to induce the expression of the Pea3 subfamily of ETS transcription factors, which comprise three members: Etv1, Etv4, and Etv5. Previous studies of our group showed that Etv4 and Etv5 are expressed by developing TrkA DRG neurons and are induced by peripheral NGF. Moreover, downregulation of Etv4 or Etv5 reduces DRG axonal growth inresponse to NGF in vitro. These results lead us to study TrkA sensory neuron population in the DRG in vivo and the target tissue innervation of peptidergic neurons.In the present study, we analyzed the in vivo role of Pea3 on the development of DRG, target innervation and its role in nociception. We investigated the consequence of disturbed Etv4 mediated signaling for pain sensation using different nociception assays such as the hot plate test, tail flick and formalin test. The results obtained by behavioral assays correlate with defects in target innervation observed in mutant mice. Our data indicates that Etv4 has a key role in sensing noxious nociceptive stimuli.