NFIL3 and cAMP Response Element-Binding Protein Form a Transcriptional Feedforward Loop that Controls Neuronal Regeneration-Associated Gene Expression

Harold D. MacGillavry, Floor J. Stam, Marion M. Sassen, Linde Kegel, William T. J. Hendriks, Joost Verhaagen, August B. Smit, Ronald E. van Kesteren*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)15542-15550
Number of pages9
JournalJournal of Neuroscience
Volume29
Issue number49
DOIs
Publication statusPublished - 9 Dec 2009

Keywords / Materials (for Non-textual outputs)

  • GENOME-WIDE ANALYSIS
  • PRO-B LYMPHOCYTES
  • AXON REGENERATION
  • CYCLIC-AMP
  • REGULATORY NETWORKS
  • NEURITE OUTGROWTH
  • SIGNAL TRANSDUCER
  • SENSORY NEURONS
  • ADULT NEURONS
  • TARGET GENE

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