期刊
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY
卷 155, 期 2, 页码 172-182出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cbpa.2009.10.042
关键词
Optic nerve regeneration; Zebrafish; ATF3; Differential gene expression; cAMP; Oligodendrocytes; Astrocytes; Retinal ganglion cells
资金
- NSF [IOB-0615762, DBI-0821252]
- Texas State Research Enhancement
- Department of Biology and College of Science at Texas State University-San Marcos
Fish, unlike mammals, can regenerate axons in the optic nerve following optic nerve injury. We hypothesized that using microarray analysis to compare gene expression in fish which had experienced optic nerve lesion to fish which had undergone a similar operation but without optic nerve injury would reveal genes specifically involved in responding to optic nerve injury (including repair), reducing detection of genes involved in the general stress and inflammatory responses. We discovered 120 genes were significantly (minimally two-fold with a P-value <= 0.05) differentially expressed (up or down) at one or more time point. Among these was ATF3, a member of the cAMP-response element binding protein family. Work by others has indicated that elevated cAMP could be important in axon regeneration. We investigated ATF3 expression further by qRT-PCR, in situ hybridization and immunohistochemistry and found ATF3 expression is significantly upregulated in the ganglion cell layer of the retina, the nerve fiber layer and the optic nerve of the injured eye. The upregulation in retina is detectable by qRT-PCR by 24 h after injury, at which time ATF-3 mRNA levels are 8-fold higher than in retinas from sham-operated fish. We conclude ATF3 may be an important mediator of optic nerve regeneration-promoting gene expression in fish, a role which merits further investigation. (C) 2009 Elsevier Inc. All rights reserved.
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