ABSTRACT
Objective To investigate the reaction of the limbs treated with different concentration of Trichostatin A(75?mol/L,750 ?mol/L,1.5mmol/L),a histone deacetylase(HDAC)-inhibitor.This may be useful to improve our understanding of the role of chromatin remodelling and epigenetic control of gene expression patterns and ultimately the development of drugs against cancer. Methods Using the chicken embryonic limb as an experimental model.The embryos received grafts of TSA soaked beads or PBS control beads into the right forelimb buds.Then they were submitted to in situ hybridization with probes and apoptosis test.Results TSA could modulate the expression of some myogenesis related genes,MyoD and Myf5 during chicken myogenesis.Using apoptosis staining methods,there was no significant apoptosis in the TSA(75?mol/L) treated embryos.However the induction of morphological changes and apoptosis at specific stage was possible with high concentration of TSA.Conclusion TSA(75?mol/L) regulates certain important transcriptional targets and strongly control muscle differentiation.Increasing the concentration of TSA(≥750?mol/L) can induce apoptosis and embryonic limb malformations.Chicken limb development can serve as a convenient in vivo model for studying the effect of HDAC inhibitors.