Lee Hyun-Shik, Bong Yong-Sik, Moore Kathryn B, Soria Kathleen, Moody Sally A, Daar Ira O
Laboratory of Protein Dynamics and Signaling, National Cancer Institute-Frederick, Frederick, MD 21702, USA.
Nat Cell Biol. 2006 Jan;8(1):55-63. doi: 10.1038/ncb1344. Epub 2005 Dec 18.
An important step in retinal development is the positioning of progenitors within the eye field where they receive the local environmental signals that will direct their ultimate fate. Recent evidence indicates that ephrinB1 functions in retinal progenitor movement, but the signalling pathway is unclear. We present evidence that ephrinB1 signals through its intracellular domain to control retinal progenitor movement into the eye field by interacting with Xenopus Dishevelled (Xdsh), and by using the planar cell polarity (PCP) pathway. Blocking Xdsh translation prevents retinal progeny from entering the eye field, similarly to the morpholino-mediated loss of ephrinB1 (ref. 2). Overexpression of Xdsh can rescue the phenotype induced by loss of ephrinB1, and this rescue (as well as a physical association between Xdsh and ephrinB1) is completely dependent on the DEP (Dishevelled, Egl-10, Pleckstrin) domain of Xdsh. Similar gain- and loss-of-function experiments suggest that Xdsh associates with ephrinB1 and mediates ephrinB1 signalling through downstream members of the PCP pathway during eye field formation.
视网膜发育中的一个重要步骤是祖细胞在眼场中的定位,在那里它们接收将指导其最终命运的局部环境信号。最近的证据表明,ephrinB1在视网膜祖细胞运动中起作用,但信号通路尚不清楚。我们提供的证据表明,ephrinB1通过其细胞内结构域发出信号,通过与非洲爪蟾Dishevelled(Xdsh)相互作用,并利用平面细胞极性(PCP)通路来控制视网膜祖细胞向眼场的运动。阻断Xdsh的翻译可阻止视网膜后代进入眼场,这与吗啉代介导的ephrinB1缺失情况类似(参考文献2)。Xdsh的过表达可以挽救由ephrinB1缺失诱导的表型,并且这种挽救(以及Xdsh和ephrinB1之间的物理关联)完全依赖于Xdsh的DEP(Dishevelled、Egl-10、Pleckstrin)结构域。类似的功能获得和功能缺失实验表明,在眼场形成过程中,Xdsh与ephrinB1相关联,并通过PCP通路的下游成员介导ephrinB1信号传导。