IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
PEA3 TRANSPCRIPTION FACTOR FAMILY MEMBER, ETV4 AND ETV5, MEDIATE NEURITE OUTGROWTH IN RESPONSE TO NEUROTROPHINS
Autor/es:
FONTANET, P; ALSINA, F; IRALA, D; BONAFINA, A; PARATCHA, G; LEDDA, F
Lugar:
Bariloche
Reunión:
Simposio; Joint ASBMB/IUBMB SISTAM 2015 Meeting; 2015
Institución organizadora:
SISTAM 2015
Resumen:
of peripheral and central nervous system development. This family comprise 4 members: nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and neurotrophin 4 (NT4). These factors play critical roles during neuronal development supporting survival, axonal and dendritic growth, guidance, branching and neuronal plasticity of specific populations of peripheral and central nervous system neurons, via the activation of their cell-surface signaling tyrosine kinase receptors: TrkA for NGF, TrkB for BDNF and NT4; and TrkC for NT3. The identification of transcription factors and downstream target genes that mediate neurotrophin dependent neuronal differentiation and target field innervation is currently a major challenge. We have identified two genes of the Pea3 transcription factor subfamily, Etv4 and Etv5, as key players of the transcriptional program triggered by the neurotrophic factors to control neuronal differentiation. Here we show that Pea3 transcription factor family members, Etv4 and Etv5, are expressed by different neuronal populations of the peripheral and central nervous system. Real time PCR assays indicated that Etv4 and Etv5 mRNA are significatively induced by the neurotrophins NGF and BDNF in sensory and hippocampal cells respectively, suggesting that they could be involved in the biological responses triggered by these neurotrophic factor molecules. Pharmacological assays revealed that activation of MEK/ERK (MAPK) pathway is required for Etv4 and Etv5 gene induction in response to neurotrophins. Gain and loss of function assays indicated that these transcription factors play an essential role in the establishment of sensory and hippocampal connectivity. In particular, downregulation of Etv4 or Etv5 in hippocampal neurons, which express endogenous levels of both transcription factors, resulted in reduced complexity of dendritic arborization and a prominent reduction of spine density, while overexpression of Etv4 and Etv5 resulted in an enhanced dendritic growth and spine development. We also provide evidence of the physiological relevance of these factors in nervous system development by analysis of transgenic mice deficient in these molecules. Together, these data establish Etv4 and Etv5 as essential molecules of the transcriptional program linking NGF and BDNF signaling to sensory and hippocampal neuronal differentiation.