Faculty Collaboration Database

Gene expression analysis of zebrafish retinal ganglion cells during optic nerve regeneration identifies KLF6a and KLF7a as important regulators of axon regeneration. Dev Biol 2007 Dec 15;312(2):596-612

Date

10/24/2007

Pubmed ID

17949705

DOI

10.1016/j.ydbio.2007.09.019

Scopus ID

2-s2.0-36549068204 (requires institutional sign-in at Scopus site)   147 Citations

Abstract

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.

Author List

Veldman MB, Bemben MA, Thompson RC, Goldman D

Author

Matthew B. Veldman PhD Associate Professor in the Cell Biology Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Axons
Gene Expression Regulation
High Mobility Group Proteins
Nerve Regeneration
Nerve Tissue Proteins
Optic Nerve
Optic Nerve Injuries
Retinal Ganglion Cells
SOX Transcription Factors
SOXC Transcription Factors
Zebrafish
Zebrafish Proteins