Eye and neural defects associated with loss of GDF6.
Eye and neural defects associated with loss of GDF6.
复制标题
与GDF6丧失有关的眼睛和神经缺陷。
DOI：
10.1186/1471-213x-6-43
复制
发表时间：
2006-09-29
影响因子：
--
通讯作者：
Hensey, Carmel
中科院分区：
文献类型：
--
作者：
Hanel, Meredith L.;Hensey, Carmel
爪蟾的骨形态发生蛋白生长与分化因子6 （GDF6）表达于神经板边缘和前神经板内，包括视野。在这里，我们通过morpholino敲除实验来研究GDF6在神经和眼睛发育中的作用。我们发现GDF6 （BMP13）的缺失导致眼睛大小缩小，层状结构丧失和视网膜内分化神经细胞类型减少。这与Smad1/5/8磷酸化染色减少相关，表明通过丢失这些骨形态发生蛋白（BMP）信号传导的细胞内介质的磷酸化，GDF6信号传导减少。此外，Pax6表达域在视神经囊泡早期减小。神经细胞粘附分子（NCAM）沿神经管的强度普遍降低，而在视网膜和大脑中，NCAM表达的离散斑块也丢失。通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）染色检测，GDF6敲低导致神经管和视网膜内细胞死亡增加。我们的数据表明，GDF6在眼睛和中枢神经系统的神经分化中具有重要作用，并且在细胞程序性死亡的正常波中，GDF6可能以某种方式维持外胚层内的细胞存活。
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. 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. 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.