Journal
JOURNAL OF NEUROSCIENCE
Volume 29, Issue 49, Pages 15542-15550Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3938-09.2009
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Funding
- Dutch Ministry of Economic Affairs [ISO52022]
- Center for Medical Systems Biology (CMSB)
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Successful regeneration of damaged neurons depends on the coordinated expression of neuron-intrinsic genes. At present however, there is no comprehensive view of the transcriptional regulatory mechanisms underlying neuronal regeneration. We used high-content cellular screening to investigate the functional contribution of 62 transcription factors to regenerative neuron outgrowth. Ten transcription factors are identified that either increase or decrease neurite outgrowth. One of these, NFIL3, is specifically upregulated during successful regeneration in vivo. Paradoxically however, knockdown of NFIL3 and overexpression of dominant-negative NFIL3 both increase neurite outgrowth. Our data show that NFIL3, together with CREB, forms an incoherent feedforward transcriptional regulatory loop in which NFIL3 acts as a negative regulator of CREB-induced regeneration-associated genes.
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