Pea3 Transcription Factor Family Members Etv4 and Etv5 Mediate Retrograde Signaling and Axonal Growth of DRG Sensory Neurons in Response to NGF

Journal Article

Nerve growth factor (NGF) is a target-derived neurotrophic growth factor that controls many aspects of sensory and sympathetic neuronal development. The identification of transcription factors and downstream target genes that mediate NGF-dependent neuronal differentiation and target field innervation is currently a major challenge. Here, we show that the Pea3 transcription factor family members Etv4 and Etv5 are expressed by developing TrkA-positive dorsal root ganglion (DRG) neurons during the period of target innervation. Real-time PCR assays indicated thatEtv4andEtv5mRNAs are significantly induced by NGF in different neuronal cells, suggesting that they could be involved in the biological responses induced by this neurotrophin. Interestingly, distal axon application of NGF in compartmentalized cultures of rat DRG sensory neurons was sufficient to induce a significant increase inEtv4andEtv5mRNA expression. Pharmacological assays also revealed that activation of MEK/ERK (MAPK) pathway is required forEtv4andEtv5gene induction in response to NGF. Downregulation of Etv4 and Etv5 using small interference RNA knockdown experiments inhibited NGF-induced neurite outgrowth of rat sensory neurons, while overexpression of full-length Etv4 or Etv5 potentiated neuronal differentiation in response to this neurotrophin. Together, these data establish Etv4 and Etv5 as essential molecules of the transcriptional program linking neurotrophin signaling to sensory neuronal differentiation, and suggest that they can be involved in NGF-mediated target innervation.

Full Text

Duke Authors

Cited Authors

  • Fontanet, P; Irala, D; Alsina, FC; Paratcha, G; Ledda, F

Published Date

  • October 2, 2013

Published In

Volume / Issue

  • 33 / 40

Start / End Page

  • 15940 - 15951

Published By

Electronic International Standard Serial Number (EISSN)

  • 1529-2401

International Standard Serial Number (ISSN)

  • 0270-6474

Digital Object Identifier (DOI)

  • 10.1523/jneurosci.0928-13.2013


  • en