Saad Kawakeb, Theis Susanne, Otto Anthony, Luke Graham, Patel Ketan
School of Biological Sciences, University of Reading, Reading, UK.
School of Biological Sciences, University of Reading, Reading, UK; Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Freiburg, Germany.
Gene. 2017 Apr 30;610:71-79. doi: 10.1016/j.gene.2017.02.012. Epub 2017 Feb 10.
The development of vertebrate appendages, especially the limb and feather buds are orchestrated by numerous secreted signalling molecules including Sonic Hedgehog, Bone Morphogenetic Proteins, Fibroblast Growth Factors and Wnts. These proteins coordinate the growth and patterning of ectodermal and mesenchymal cells. The influence of signalling molecules is affected over large distances by their concentration (morphogen activity) but also at local levels by the presence of proteins that either attenuate or promote their activity. Glypicans are cell surface molecules that regulate the activity of the major secreted signalling molecules expressed in the limb and feather bud. Here we investigated the expression of all Glypicans during chick limb and feather development. In addition we profiled the expression of Notum, an enzyme that regulates Glypican activity. We show that five of the six Glypicans and Notum are expressed in a dynamic manner during the development of limbs and feathers. We also investigated the expression of key Glypicans and show that they are controlled by signalling molecules highlighting the presence of feedback loops. Lastly we show that Glypicans and Notum are expressed in a tissue specific manner in adult chicken tissues. Our results strongly suggest that the Glypicans and Notum have many as yet undiscovered roles to play during the development of vertebrate appendages.
脊椎动物附肢的发育,尤其是肢体和羽毛芽的发育,是由众多分泌信号分子精心调控的,这些分子包括音猬因子、骨形态发生蛋白、成纤维细胞生长因子和Wnt蛋白。这些蛋白质协调外胚层和间充质细胞的生长与模式形成。信号分子的影响在远距离上受其浓度(形态发生素活性)的影响,在局部水平上也受减弱或促进其活性的蛋白质的存在的影响。磷脂酰肌醇蛋白聚糖是调节肢体和羽毛芽中表达的主要分泌信号分子活性的细胞表面分子。在此,我们研究了所有磷脂酰肌醇蛋白聚糖在鸡肢体和羽毛发育过程中的表达。此外,我们分析了Notum的表达情况,Notum是一种调节磷脂酰肌醇蛋白聚糖活性的酶。我们发现六种磷脂酰肌醇蛋白聚糖中的五种以及Notum在肢体和羽毛发育过程中以动态方式表达。我们还研究了关键磷脂酰肌醇蛋白聚糖的表达,发现它们受信号分子控制,这突出了反馈回路的存在。最后,我们表明磷脂酰肌醇蛋白聚糖和Notum在成年鸡组织中以组织特异性方式表达。我们的结果强烈表明,磷脂酰肌醇蛋白聚糖和Notum在脊椎动物附肢发育过程中还有许多尚未被发现的作用。