Pea3 transcription factors, Etv4 and Etv5, are mediators of BDNF-mediated hippocampal dendrite growth during development

FONTANET, P; ALSINA, F; IRALA, D; BONAFINA; PARATCHA, G.; LEDDA, F

Rosario

Congreso; L Congreso Anual de la SOciedad Argentina de BIoquimica y Biología Molecular; 2014

Sociedad Argentina de Investigacion Bioquímica y Biología Molecular

The precise development of complex and specific dendrite morphology is essential in the development of the functional properties of neural circuits and many neurodevelopmental disorders are due to structural abnormalities of dendrites and their connections. In the present work, we show that two members of the Pea3 family of transcriptional factors, Etv4 and Etv5, are key regulators of growth and elaboration of pyramidal cell dendrites in the developing hippocampus. We show that hippocampal neurons co-express Etv4 and Etv5 during development. Downregulation of Etv4 and Etv5 in pyramidal neurons, which express endogenous levels of both transcription factors, resulted in reduced complexity of dendritic arborization and a prominent reduction of spine density. Overexpression of Etv4 and Etv5 resulted in an enhanced dendritic growth and spine development. We also provide evidence indicating that the induction of Etv4 and Etv5 by the Brain Derived Neurotrophic Factor (BDNF) is essential to control dendrite patterning. Our experimental data support the idea that BDNF induce transcriptional programs, which involve Etv4 and Etv5, which play a crucial role in the establishment of hippocampal connectivity.