Pea3 transcription factor family members Etv4 and Etv5 mediate retrograde signaling and axonal growth of DRG sensory neurons in response to NGF
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 innervatio...
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paper:paper_02706474_v33_n40_p15940_Fontanet2023-06-08T15:24:51Z Pea3 transcription factor family members Etv4 and Etv5 mediate retrograde signaling and axonal growth of DRG sensory neurons in response to NGF 2 (2 amino 3 methoxyphenyl) chromone collagenase 3 mitogen activated protein kinase nerve growth factor protein tyrosine kinase A stromelysin transcription factor transcription factor ER81 transcription factor etv4 transcription factor ETV5 unclassified drug animal cell animal tissue article cell survival controlled study down regulation embryo gene expression genetic transfection immunofluorescence nerve cell differentiation nerve fiber growth nonhuman priority journal rat real time polymerase chain reaction RNA interference sensory nerve cell signal transduction spinal ganglion Western blotting Animals Axons Chick Embryo DNA-Binding Proteins Ganglia, Spinal Nerve Growth Factor PC12 Cells Rats Rats, Wistar Sensory Receptor Cells Trans-Activators Transcription Factors 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 that Etv4 and Etv5 mRNAs 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 in Etv4 and Etv5 mRNA expression. Pharmacological assays also revealed that activation of MEK/ERK (MAPK) pathway is required for Etv4 and Etv5 gene induction in response to NGF. Downregulation of Etv4 and Etv5 using small interference RNA knockdown experiments inhibited NGFinduced 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. © 2013 the authors. 2013 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v33_n40_p15940_Fontanet http://hdl.handle.net/20.500.12110/paper_02706474_v33_n40_p15940_Fontanet |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
2 (2 amino 3 methoxyphenyl) chromone collagenase 3 mitogen activated protein kinase nerve growth factor protein tyrosine kinase A stromelysin transcription factor transcription factor ER81 transcription factor etv4 transcription factor ETV5 unclassified drug animal cell animal tissue article cell survival controlled study down regulation embryo gene expression genetic transfection immunofluorescence nerve cell differentiation nerve fiber growth nonhuman priority journal rat real time polymerase chain reaction RNA interference sensory nerve cell signal transduction spinal ganglion Western blotting Animals Axons Chick Embryo DNA-Binding Proteins Ganglia, Spinal Nerve Growth Factor PC12 Cells Rats Rats, Wistar Sensory Receptor Cells Trans-Activators Transcription Factors |
spellingShingle |
2 (2 amino 3 methoxyphenyl) chromone collagenase 3 mitogen activated protein kinase nerve growth factor protein tyrosine kinase A stromelysin transcription factor transcription factor ER81 transcription factor etv4 transcription factor ETV5 unclassified drug animal cell animal tissue article cell survival controlled study down regulation embryo gene expression genetic transfection immunofluorescence nerve cell differentiation nerve fiber growth nonhuman priority journal rat real time polymerase chain reaction RNA interference sensory nerve cell signal transduction spinal ganglion Western blotting Animals Axons Chick Embryo DNA-Binding Proteins Ganglia, Spinal Nerve Growth Factor PC12 Cells Rats Rats, Wistar Sensory Receptor Cells Trans-Activators Transcription Factors Pea3 transcription factor family members Etv4 and Etv5 mediate retrograde signaling and axonal growth of DRG sensory neurons in response to NGF |
topic_facet |
2 (2 amino 3 methoxyphenyl) chromone collagenase 3 mitogen activated protein kinase nerve growth factor protein tyrosine kinase A stromelysin transcription factor transcription factor ER81 transcription factor etv4 transcription factor ETV5 unclassified drug animal cell animal tissue article cell survival controlled study down regulation embryo gene expression genetic transfection immunofluorescence nerve cell differentiation nerve fiber growth nonhuman priority journal rat real time polymerase chain reaction RNA interference sensory nerve cell signal transduction spinal ganglion Western blotting Animals Axons Chick Embryo DNA-Binding Proteins Ganglia, Spinal Nerve Growth Factor PC12 Cells Rats Rats, Wistar Sensory Receptor Cells Trans-Activators Transcription Factors |
description |
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 that Etv4 and Etv5 mRNAs 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 in Etv4 and Etv5 mRNA expression. Pharmacological assays also revealed that activation of MEK/ERK (MAPK) pathway is required for Etv4 and Etv5 gene induction in response to NGF. Downregulation of Etv4 and Etv5 using small interference RNA knockdown experiments inhibited NGFinduced 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. © 2013 the authors. |
title |
Pea3 transcription factor family members Etv4 and Etv5 mediate retrograde signaling and axonal growth of DRG sensory neurons in response to NGF |
title_short |
Pea3 transcription factor family members Etv4 and Etv5 mediate retrograde signaling and axonal growth of DRG sensory neurons in response to NGF |
title_full |
Pea3 transcription factor family members Etv4 and Etv5 mediate retrograde signaling and axonal growth of DRG sensory neurons in response to NGF |
title_fullStr |
Pea3 transcription factor family members Etv4 and Etv5 mediate retrograde signaling and axonal growth of DRG sensory neurons in response to NGF |
title_full_unstemmed |
Pea3 transcription factor family members Etv4 and Etv5 mediate retrograde signaling and axonal growth of DRG sensory neurons in response to NGF |
title_sort |
pea3 transcription factor family members etv4 and etv5 mediate retrograde signaling and axonal growth of drg sensory neurons in response to ngf |
publishDate |
2013 |
url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v33_n40_p15940_Fontanet http://hdl.handle.net/20.500.12110/paper_02706474_v33_n40_p15940_Fontanet |
_version_ |
1768546539653824512 |