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Zusammenfassung:
Epimorphic regeneration of new tissue requires initiating and controlling extensive cell proliferation after partial loss of an organ or appendage. It is unclear what the molecular determinants are that coordinate cell proliferation with patterning of the tissues during tissue regeneration. We found that fam53b/simplet (smp) regulates both cell proliferation and the transcription of specific genes that are associated with tissue patterning. In situ hybridization and quantitative RT-PCR experiments showed that amputation of zebrafish hearts and fins resulted in expression of the smp gene. In regenerating adult fins, we observed smp expression in the distal mesenchyme which later expanded to the basal layers of the distal epidermis and distal tip epithelium. While we observed significant up-regulation of the gene in regenerating tissues, we did not detect its expression during the growth phase of juvenile fins, indicating that the activation of the smp gene is associated with a transcriptional program that is different from that used for the developmental outgrowth of larval and juvenile fins. Morpholino knockdown of smp significantly reduced regenerative outgrowth by decreasing cell proliferation as measured by BrdU incorporation and histone-3 phosphorylation. In addition, smp knockdown increased the expression of msxb, msxc, and shh, suggesting that loss of smp de-repressed genes associated with patterning of the regenerating tissues. In accordance, loss of smp resulted in the formation of ectopic bone. Taken together, these data indicate a requirement for smp in fin regeneration through control of cell proliferation, for the regulation of specific genes and for proper patterning.
