Gene expression analysis of zebrafish retinal ganglion cells during optic nerve regeneration identifies KLF6a and KLF7a as important regulators of axon regeneration.
Unlike mammals, teleost fish are able to mount an efficient and robust regenerative response following optic nerve injury. Although it is clear that changes in gene expression accompany axonal regeneration, the extent of this genomic response is not known. To identify genes involved in successful nerve regeneration, we analyzed gene expression in zebrafish retinal ganglion cells (RGCs) regenerating their axons following optic nerve injury. Microarray analysis of RNA isolated by laser capture microdissection from uninjured and 3-day post-optic nerve injured RGCs identified 347 up-regulated and 29 down-regulated genes. Quantitative RT-PCR and in situ hybridization were used to verify the change in expression of 19 genes in this set. Gene ontological analysis of the data set suggests regenerating neurons up-regulate genes associated with RGC development. However, not all regeneration-associated genes are expressed in differentiating RGCs indicating the regeneration is not simply a recapitulation of development. Knockdown of six highly induced regeneration-associated genes identified two, KLF6a and KLF7a, that together were necessary for robust RGC axon re-growth. These results implicate KLF6a and KLF7a as important mediators of optic nerve regeneration and suggest that not all induced genes are essential to mount a regenerative response.
Veldman
Matthew B
MB
Neuroscience Program, University of Michigan, 5045 Biomedical Sciences Research Building, 109 Zina Pitcher Place, Ann Arbor, MI 48109, USA.
Bemben
Michael A
MA
Thompson
Robert C
RC
Goldman
Daniel
D
D000818:Animals; D001369:Axons / Q000502:physiology*; D005786:Gene Expression Regulation; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism; D009416:Nerve Regeneration / Q000235:genetics* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009900:Optic Nerve / Q000502:physiology*; D020221:Optic Nerve Injuries / Q000235:genetics / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D055747:SOX Transcription Factors; D055751:SOXC Transcription Factors; D015027:Zebrafish / Q000235:genetics / Q000502:physiology; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D006609:High Mobility Group Proteins; C525954:KLF6a protein, zebrafish; C525955:KLF7a protein, zebrafish; D009419:Nerve Tissue Proteins; D055747:SOX Transcription Factors; D055751:SOXC Transcription Factors; D029961:Zebrafish Proteins; C490794:sox11a protein, zebrafish; C490795:sox11b protein, zebrafish