Unraveling Tissue Regeneration Using Chemical Genetics
Unraveling tissue regeneration using chemical genetics by Lijoy K. Mathew Understanding the advantages of chemicals to probe tissue regeneration, we developed a rapid throughput regeneration assay to identify additional small molecules that modulated regeneration. Glucocort.... Published date on: 2008 with total page: 200 pages. Publisher of Unraveling Tissue Regeneration Using Chemical Genetics is ProQuest.
Understanding the advantages of chemicals to probe tissue regeneration, we developed a rapid throughput regeneration assay to identify additional small molecules that modulated regeneration. Glucocorticoids were identified as inhibitors of regeneration and we demonstrated that glucocorticoid receptor activation is absolutely required for mediating the inhibition of regeneration. We further illustrated that, signaling from exogenous glucocorticoids impairs blastema formation and limits regenerative capability in vertebrates through an acute inflammation-independent mechanism and also report that, neutrophils and macrophages are not required for fin regeneration. Finally, we performed a comparative global genomic analysis between different zebrafish regeneration models and identified raldh2, a rate limiting enzyme for retinoic acid (RA) synthesis as a candidate gene across the distinct regeneration models. We demonstrated that, in addition to the well established role of RA signaling during the later phase of regenerative outgrowth, this signaling pathway is also critical for the initiation of regeneration, suggesting a dual phase of RA signaling during fin regeneration. Collectively, our results obtained through different experimental approaches suggest that, epimorphic regeneration is completed by a well orchestrated process of multiple molecular signaling events.
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