Plautz Carol Zygar, Zirkle Brett E, Deshotel Malia J, Grainger Robert M
Shepherd University, Department of Biology, Shepherdstown, West Virginia.
Dev Dyn. 2014 Dec;243(12):1606-18. doi: 10.1002/dvdy.24193. Epub 2014 Oct 18.
Specific molecules involved in early inductive signaling from anterior neural tissue to the placodal ectoderm to establish a lens-forming bias, as well as their regulatory factors, remain largely unknown. In this study, we sought to identify and characterize these molecules.
Using an expression cloning strategy to isolate genes with lens-inducing activity, we identified the transcriptional cofactor ldb1. This, together with evidence for its nuclear dependence, suggests its role as a regulatory factor, not a direct signaling molecule. We propose that ldb1 mediates induction of early lens genes in our functional assay by transcriptional activation of lens-inducing signals. Gain-of-function assays demonstrate that the inductive activity of the anterior neural plate on head ectodermal structures can be augmented by ldb1. Loss-of-function assays show that knockdown of ldb1 leads to decreased expression of early lens and retinal markers and subsequently to defects in eye development.
The functional cloning, expression pattern, overexpression, and knockdown data show that an ldb1-regulated mechanism acts as an early signal for Xenopus lens induction.
从神经前体细胞到基板外胚层早期诱导信号中涉及的特定分子，以及建立晶状体形成倾向的调节因子，目前仍不清楚。在本研究中，我们试图鉴定和表征这些分子。
利用表达克隆策略分离具有晶状体诱导活性的基因，我们鉴定出转录辅因子ldb1。这一结果以及其对细胞核的依赖性表明，它作为一种调节因子，而非直接信号分子发挥作用。我们认为，在我们的功能试验中，ldb1通过转录激活晶状体诱导信号来介导早期晶状体基因的诱导。功能获得试验表明，ldb1可增强神经前板对头外胚层结构的诱导活性。功能丧失试验表明，ldb1的敲低导致早期晶状体和视网膜标志物的表达下降，并随后导致眼发育缺陷。
功能克隆、表达模式、过表达和敲低数据表明，一种ldb1调节机制作为非洲爪蟾晶状体诱导的早期信号发挥作用。
