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

被引：62

作者：

MacGillavry, Harold D. ^{[1
]}

Stam, Floor J. ^{[1
]}

Sassen, Marion M. ^{[1
]}

Kegel, Linde ^{[1
]}

Hendriks, William T. J. ^{[1
]}

Verhaagen, Joost ^{[2
]}

Smit, August B. ^{[1
]}

van Kesteren, Ronald E. ^{[1
]}

机构：

[1] Vrije Univ Amsterdam, Dept Mol & Cellular Neurobiol, Ctr Neurogenom & Cognit Res, NL-1081 HV Amsterdam, Netherlands

[2] Netherlands Inst Neurosci, Dept Neuroregenerat, NL-1105 BA Amsterdam, Netherlands

来源：

JOURNAL OF NEUROSCIENCE | 2009年 / 29卷 / 49期

关键词：

GENOME-WIDE ANALYSIS; AXONAL GROWTH; CYCLIC-AMP; NEURITE OUTGROWTH; SIGNAL TRANSDUCER; TARGET GENE; SPINAL-CORD; CELL-LINE; C-JUN; EVOLUTION;

D O I：

10.1523/JNEUROSCI.3938-09.2009

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：15542 / 15550

页数：9

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