NFIL3 and cAMP response element-binding protein form a transcriptional feedforward loop that controls neuronal regeneration-associated gene expression

H.D. Mac Gillavry, F.J. Stam, M.J.M. Sassen, L. Kegel, W.T.J. Hendriks, J. Verhaagen, A.B. Smit, R.E. van Kesteren

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Abstract

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.Weused 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. Copyright © 2009 Society for Neuroscience.
Original languageEnglish
Pages (from-to)15542-15550
Number of pages8
JournalThe Journal of Neuroscience
Volume29
Issue number49
DOIs
Publication statusPublished - 2009

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