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ToxSci Advance Access originally published online on January 27, 2006
Toxicological Sciences 2006 92(1):254-269; doi:10.1093/toxsci/kfj118
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

HIGHLIGHTED ARTICLE

Regenerative Growth Is Impacted by TCDD: Gene Expression Analysis Reveals Extracellular Matrix Modulation

Eric A. Andreasen, Lijoy K. Mathew and Robert L. Tanguay1

Department of Environmental and Molecular Toxicology, Environmental Health Sciences Center, Marine and Freshwater Biomedical Sciences Center, Oregon State University, Corvallis, Oregon 97331

Received November 28, 2005; accepted January 20, 2006

Adult zebrafish can completely regenerate their caudal fin following amputation. This complex process is initiated by the formation of an epithelial wound cap over the amputation site by 12 h post amputation (hpa). Once the cap is formed, mesenchymal cells proliferate and migrate from sites distal to the wound plane and accumulate under the epithelial cap forming the blastemal structure within 48 hpa. Blastemal cells proliferate and differentiate, replacing the amputated tissues, which are populated with angiogenic vessels and innervating nerves during the regenerative outgrowth phase which is completed around 14 days post amputation (dpa). Regenerative outgrowth does not occur in TCDD-exposed zebrafish. To identify the molecular pathways that are perturbed by TCDD exposure, male zebrafish were ip injected with 50 ng/g TCDD or vehicle and caudal fins were amputated. Regenerating fin tissue was collected at 1, 3, and 5 dpa for mRNA abundance analysis. Microarray analysis and quantitative real time PCR revealed that wound healing and regeneration alone altered the expression of nearly 900 genes by at least two-fold between 1 and 5 dpa. TCDD altered the abundance of 370 genes at least two-fold. Among these, several known aryl hydrocarbon responsive genes were identified in addition to several genes involved in extracellular matrix composition and metabolism. The profile of misexpressed genes is suggestive of impaired cellular differentiation and extracellular matrix composition potentially regulated by Sox9b.

Key Words: AHR; TCDD; regeneration; zebrafish; extracellular matrix.


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