BACKGROUND:In Xenopus the bone morphogenetic protein growth and differentiation factor 6 (GDF6) is expressed at the edge of the neural plate, and within the anterior neural plate including the eye fields. Here we address the role of GDF6 in neural and eye development by morpholino knockdown experiments. RESULTS:We show that depletion of GDF6 (BMP13) resulted in a reduction in eye size, loss of laminar structure and a reduction in differentiated neural cell types within the retina. This correlated with a reduction in staining for Smad1/5/8 phosphorylation indicating a decrease in GDF6 signalling through loss of phosphorylation of these intracellular mediators of bone morphogenetic protein (BMP) signalling. In addition, the Pax6 expression domain is reduced in size at early optic vesicle stages. Neural cell adhesion molecule (NCAM) is generally reduced in intensity along the neural tube, while in the retina and brain discreet patches of NCAM expression are also lost. GDF6 knock down resulted in an increase in cell death along the neural tube and within the retina as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. CONCLUSION:Our data demonstrate that GDF6 has an important role in neural differentiation in the eye as well as within the central nervous system, and that GDF6 may act in some way to maintain cell survival within the ectoderm, during the normal waves of programmed cell death.

译文

背景:在非洲爪蟾中,骨形态发生蛋白生长和分化因子6(GDF6)在神经板的边缘以及包括眼野在内的前神经板内表达。在这里,我们通过吗啉代敲除实验解决了GDF6在神经和眼睛发育中的作用。
结果:我们显示,GDF6(BMP13)耗竭导致眼睛大小减少,层状结构丧失以及视网膜内分化的神经细胞类型减少。这与Smad1 / 5/8磷酸化染色的减少有关,表明通过骨形态发生蛋白(BMP)信号传导的这些细胞内介质的磷酸化损失,GDF6信号传导减少。此外,Pax6表达域的大小在早期的囊泡阶段被减小。神经细胞粘附分子(NCAM)沿神经管的强度通常会降低,而在视网膜和大脑中,NCAM表达的谨慎斑块也会丢失。通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)染色确定,GDF6敲低导致沿神经管和视网膜内细胞死亡增加。
结论:我们的数据表明,GDF6在眼睛以及中枢神经系统内的神经分化中具有重要作用,并且在正常的程序性细胞死亡浪潮中,GDF6可能以某种方式维持外胚层中的细胞存活。 。

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