Saad Kawakeb, Otto Anthony, Theis Susanne, Kennerley Niki, Munsterberg Andrea, Luke Graham, Patel Ketan
School of Biological Sciences, University of Reading, Reading, UK.
School of Biological Sciences, Norwich Research Park, University of East Anglia, Norwich, NR4 7TJ.
Gene. 2017 Apr 20;609:38-51. doi: 10.1016/j.gene.2017.01.032. Epub 2017 Feb 2.
Vertebrate development is orchestrated by secreted signalling molecules that regulate cell behaviour and cell fate decisions during early embryogenesis. The activity of key signalling molecules including members of Hedgehog, Bone Morphogenetic Proteins and Wnt families are regulated by Glypicans, a family of GPI linked polypeptides. Glypicans either promote or inhibit the action of signalling molecules and add a layer of complexity that needs to be understood in order to fully decipher the processes that regulate early vertebrate development. Here we present a detailed expression profile of all six Glypicans and their modifying enzyme Notum during chick embryogenesis. Our results strongly suggest that these proteins have many as yet undiscovered roles to play during early embryogenesis. Finally, we have taken an experimental approach to investigate their role during the patterning of a key embryonic structure - the neural tube. In particular, we show that over-expression of Notum leads to the dorsalisation of this structure.
脊椎动物的发育由分泌的信号分子精心调控，这些信号分子在早期胚胎发育过程中调节细胞行为和细胞命运决定。包括刺猬因子家族、骨形态发生蛋白家族和Wnt家族成员在内的关键信号分子的活性，受Glypicans（一类糖基磷脂酰肌醇连接的多肽）调控。Glypicans既能促进也能抑制信号分子的作用，增加了一层复杂性，为了全面解读调控早期脊椎动物发育的过程，这一点需要被理解。在此，我们展示了所有六种Glypicans及其修饰酶Notum在鸡胚胎发育过程中的详细表达谱。我们的结果强烈表明，这些蛋白质在早期胚胎发育过程中还有许多尚未被发现的作用。最后，我们采用实验方法研究了它们在关键胚胎结构——神经管的模式形成过程中的作用。特别是，我们发现Notum的过表达会导致该结构背侧化。
