Abstract
BackgroundAmong the vertebrates, teleost and urodele amphibians are capable of regenerating their central nervous system. We have used zebrafish as a model to study spinal cord injury and regeneration. Relatively little is known about the molecular mechanisms underlying spinal cord regeneration and information based on high density oligonucleotide microarray was not available. We have used a high density microarray to profile the temporal transcriptome dynamics during the entire phenomenon.ResultsA total of 3842 genes expressed differentially with significant fold changes during spinal cord regeneration. Cluster analysis revealed event specific dynamic expression of genes related to inflammation, cell death, cell migration, cell proliferation, neurogenesis, neural patterning and axonal regrowth. Spatio-temporal analysis of stat3 expression suggested its possible function in controlling inflammation and cell proliferation. Genes involved in neurogenesis and their dorso-ventral patterning (sox2 and dbx2) are differentially expressed. Injury induced cell proliferation is controlled by many cell cycle regulators and some are commonly expressed in regenerating fin, heart and retina. Expression pattern of certain pathway genes are identified for the first time during regeneration of spinal cord. Several genes involved in PNS regeneration in mammals like stat3, socs3, atf3, mmp9 and sox11 are upregulated in zebrafish SCI thus creating PNS like environment after injury.ConclusionOur study provides a comprehensive genetic blue print of diverse cellular response(s) during regeneration of zebrafish spinal cord. The data highlights the importance of different event specific gene expression that could be better understood and manipulated further to induce successful regeneration in mammals.
Highlights
IntroductionUrodele amphibians and teleost fish have ability to regenerate their spinal cord after injury
Among the vertebrate, urodele amphibians and teleost fish have ability to regenerate their spinal cord after injury
Axonal regrowth can be seen in 15 dpi cord and remyelination is aided by the presence of Schwann cells. Both neurogenesis and axonogenesis is leading to successful regeneration in this species
Summary
Urodele amphibians and teleost fish have ability to regenerate their spinal cord after injury. In mammals following spinal cord injury (SCI) there are overwhelming inflammatory responses which trigger several other secondary tissue damage, neuronal and glial loss, progressive cavitation and glial scarring. These processes lead to functional decline and paralysis. Zebrafish is a powerful vertebrate model organism to elucidate gene function during regeneration, since they have extraordinary ability to regenerate their fins [1,2], heart muscle [3] and central nervous system (CNS) [4,5,6,7,8,9] after injury. We have used a high density microarray to profile the temporal transcriptome dynamics during the entire phenomenon
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