Abstracts (poster) - Wissenschaft Online

Tuan Nguyen, Mahmoud Youness, Andrea Tedeschi, Andrew Green, Kirsi Forsberg,
Simone Di Giovanni
The role of NFAT in axonal outgrowth and regeneration
Axons of the adult mammalian central nervous system (CNS) do not regenerate
following injury due to the presence of an inhibitory environment and the lack of intrinsic
pro-growth capacity. However, transcription mediated gene expression, essential for
neurite and axon outgrowth during development, is often recapitulated following axonal
injury in the peripheral nervous system, where sprouting and regeneration do occur.
The nuclear factor for activated T cells (NFAT) is a family of transcription factors that
plays a role in axon growth and guidance during neuronal development, however direct
transcriptional targets for NFAT in developing and regenerating neurons have not been
identified. We hypothesize that developmental genes regulated by NFAT might also play
a role in axon sprouting and regeneration in the adult CNS.
In search for potential NFAT transcriptional targets, we performed an in silico promoter
analysis, which revealed several putative NFAT binding sites within the promoter region
of an important pro-axon outgrowth and pro-regeneration gene, the growth associated
protein-43 (GAP-43).
Chromatin immunoprecipitation and transfection experiments showed that neuronal
enriched NFAT3 occupies the GAP-43 promoter and drives its expression in PC12 cells
and cultured primary neurons. In addition, NFAT3 is found in the nucleus and occupies
the GAP-43 promoter in the cortex during a developmental window where neurons are
actively extending axons and establishing connections (from E16 to P1). Next, we
observed that overexpression of NFAT3 promotes both GAP-43 expression and
neurite/axon outgrowth. Taken together, our data unveil a previously unknown NFAT3
dependent molecular pathway for neurite and axon outgrowth.
contact:
PhD Tuan Nguyen
Universität Tübingen
Hertie Institut
tuan.nguyen@medizin.uni-tuebingen.de
Otfried-Müllerstr. 27
72076 Tübingen (Deutschland)