Rorick Anna M, Mei Wenyan, Liette Nicole L, Phiel Christopher, El-Hodiri Heithem M, Yang Jing
Columbus Children's Research Institute, Department of Pediatrics, The Ohio State University, Columbus, OH 43205, USA.
Dev Biol. 2007 Feb 15;302(2):477-93. doi: 10.1016/j.ydbio.2006.10.011. Epub 2006 Oct 10.
Eye induction and eye field separation are the earliest events during vertebrate eye development. Both of these processes occur much earlier than the formation of optic vesicles. The insulin-like growth factor (IGF) pathway appears to be essential for eye induction, yet it remains unclear how IGF downstream pathways are involved in eye induction. As a consequence of eye induction, a single eye anlage is specified in the anterior neural plate. Subsequently, this single eye anlage is divided into two symmetric eye fields in response to Sonic Hedgehog (Shh) secreted from the prechordal mesoderm. Here, we report that B56epsilon regulatory subunit of protein phosphatase 2A (PP2A) is involved in Xenopus eye induction and subsequent eye field separation. We provide evidence that B56epsilon is required for the IGF/PI3K/Akt pathway and that interfering with the PI3K/Akt pathway inhibits eye induction. In addition, we show that B56epsilon regulates the Hedgehog (Hh) pathway during eye field separation. Thus, B56epsilon is involved in multiple signaling pathways and plays critical roles during early development.
眼诱导和眼场分离是脊椎动物眼睛发育过程中最早发生的事件。这两个过程都比视泡形成要早得多。胰岛素样生长因子(IGF)信号通路似乎对眼诱导至关重要,但IGF下游通路如何参与眼诱导仍不清楚。作为眼诱导的结果,在前神经板中确定了一个单一的眼原基。随后,响应于来自脊索前中胚层分泌的音猬因子(Shh),这个单一的眼原基被分为两个对称的眼场。在这里,我们报道蛋白磷酸酶2A(PP2A)的B56ε调节亚基参与非洲爪蟾的眼诱导及随后的眼场分离。我们提供的证据表明,B56ε是IGF/PI3K/Akt信号通路所必需的,干扰PI3K/Akt信号通路会抑制眼诱导。此外,我们表明B56ε在眼场分离过程中调节刺猬因子(Hh)信号通路。因此,B56ε参与多个信号通路,并在早期发育过程中发挥关键作用。