Canopy1, a novel regulator of FGF signaling around the midbrain-hindbrain boundary in zebrafish
Canopy1, a novel regulator of FGF signaling around the midbrain-hindbrain boundary in zebrafish
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DOI：
10.1016/j.cub.2006.01.055
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发表时间：
2006-02-21
期刊：
影响因子：
9.2
通讯作者：
Okamoto, H
中科院分区：
文献类型：
--
作者：
Hirate, Y;Okamoto, H
来自中脑-后脑边界（MHB，峡部）的FGF信号在MHB的维持和顶盖和小脑的诱导中都起着重要作用[1-3]。由于MHB中不同水平的FGF信号传导导致诱导活性[4]的质的差异，因此MHB中FGF信号传导应在多个步骤中进行严格的正向和负向调节，以确保FGF信号传导[5]的正确水平。已经报道了MHB周围FGF信号负向调节的因子[6-8]。然而，确保MHB中FGF信号强烈的因素在很大程度上是未知的。在这里，我们报道了Canopy1 （Cnpy1）的鉴定，这是一种新的mhb特异性的皂素相关蛋白，属于一个进化上保守的蛋白家族。cnpy1基因在斑马鱼胚胎MHB中特异性表达。外源性FGF8诱导颖花原始叶中cnpy1的表达。敲低cnpy1导致MHB缺陷和FGF信号以细胞自主的方式受损。Cnpy1定位于内质网并与FGFR1相互作用。本研究强调了FGFR通路和Cnpy1之间的正反馈回路，该回路可能确保MHB中FGF信号的强度，从而导致顶盖和小脑的正确发育。
FGF signaling from the midbrain-hindbrain boundary (MHB, isthmus) plays a major role both in maintenance of the MHB and induction of the tectum and cerebellum [1-3]. Since different levels of FGF signaling in the MHB result in a qualitative difference in inducing activity [4], FGF signaling in the MHB should be tightly regulated positively and negatively at multiple steps to ensure correct levels of FGF signaling [5]. Factors that negatively regulate FGF signal around the MHB are reported [6-8]. However, factors that ensure strong FGF signal in the MHB are largely unknown. Here we report the identification of Canopy1 (Cnpy1), a novel MHB-specific, Saposin-related protein that belongs to an evolutionarily conserved protein family. The cnpy1 gene was expressed specifically in the MHB of zebrafish embryos. Exogenous FGF8 induced expression of cnpy1 in the tectal primordial. Knockdown of cnpy1 resulted in MHB defects and impaired FGF signaling in a cell-autonomous manner. Cnpy1 is localized in the endoplasmic reticulum and interacts with FGFR1. This study highlights a positive-feed back loop between the FGFR pathway and Cnpy1 that may ensure the strength of FGF signaling in the MHB, leading to correct development of the tectum and cerebellum.