【摘 要】
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Mbd3 is a key component of the Nucleosome Remodelling and Histone Deacetylation(NuRD)complex,and has been found to play roles in maintaining pluripotency of
【机 构】
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Tsinghua-PekingCenterforLifeSciences,TsinghuaUniversity,Beijing100084,China
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Mbd3 is a key component of the Nucleosome Remodelling and Histone Deacetylation(NuRD)complex,and has been found to play roles in maintaining pluripotency of embryonic stem cells.However,its functions in specific tissue development remain unclear.In zebrafish,two duplicates of mbd3,mbd3a and mbd3b,have been identified,and mbd3b is highly expressed in the dorsal forerunner cells(DFCs),a group of cells which are essential for left-right pattern.We used a morpholino-mediated knockdown strategy to study mbd3b function during left-right patterning in the zebrafish embryo.Knocking down mbd3b specifically in DFCs disrupts the left-right asymmetry.This is preceded by dispersal of DFCs and abnormal formation of Kupffer’s vesicle(KV).Inhibition of the histone deacetylase(HDAC)activity by classic I HDAC inhibitor VPA perturbs the DFCs clustering and causes DFCs apoptosis.This indicates that HDAC activity is required for the DFCs clustering and survival.Moreover,knockdown of the NuRD subunits coding genes mta2 or mta3 in DFCs also randomizes the L-R pattern markers.Taking together,we propose that mbd3b is necessary for DFCs clustering and Kupffer’s vesicle(KV)organgenesis and its function within left-right asymmetry may depend on the formation of the NuRD complex.
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