Stickney Heather L, Imai Yoshiyuki, Draper Bruce, Moens Cecilia, Talbot William S
Stanford University School of Medicine, Department of Developmental Biology, Stanford, CA 94305, USA.
Dev Biol. 2007 Oct 1;310(1):71-84. doi: 10.1016/j.ydbio.2007.07.027. Epub 2007 Jul 28.
Bone morphogenetic proteins (BMPs) are key mediators of dorsoventral patterning in vertebrates and are required for the induction of ventral fates in fish and frogs. A widely accepted model of dorsoventral patterning postulates that a morphogenetic BMP activity gradient patterns cell fates along the dorsoventral axis. Recent work in zebrafish suggests that the role of BMP signaling changes over time, with BMPs required for global dorsoventral patterning during early gastrulation and for tail patterning during late gastrulation and early somitogenesis. Key questions remain about the late phase, including which BMP ligands are required and how the functions of BMPs differ during the early and late gastrula stages. In a screen for dominant enhancers of mutations in the homeobox genes vox and vent, which function in parallel to bmp signaling, we identified an insertion mutation in bmp4. We then performed a reverse genetic screen to isolate a null allele of bmp4. We report the characterization of these two alleles and demonstrate that BMP4 is required during the later phase of BMP signaling for the specification of ventroposterior cell fates. Our results indicate that different bmp genes are essential at different stages. In addition, we present genetic evidence supporting a role for a morphogenetic BMP gradient in establishing mesodermal fates during the later phase of BMP signaling.
骨形态发生蛋白(BMPs)是脊椎动物背腹模式形成的关键调节因子,也是鱼类和青蛙腹侧命运诱导所必需的。一个被广泛接受的背腹模式形成模型假定,一种形态发生性BMP活性梯度沿着背腹轴决定细胞命运。斑马鱼的近期研究表明,BMP信号传导的作用随时间而变化,在原肠胚形成早期,BMPs参与整体背腹模式形成,而在原肠胚形成后期和早期体节形成阶段则参与尾部模式形成。关于后期阶段仍存在关键问题,包括需要哪些BMP配体,以及BMPs在原肠胚早期和晚期阶段的功能有何不同。在对与bmp信号传导平行发挥作用的同源盒基因vox和vent突变的显性增强子进行筛选时,我们鉴定出bmp4中的一个插入突变。然后我们进行了反向遗传筛选以分离bmp4的无效等位基因。我们报告了这两个等位基因的特征,并证明在BMP信号传导的后期阶段,BMP4是腹后细胞命运特化所必需的。我们的结果表明,不同的bmp基因在不同阶段至关重要。此外,我们提供了遗传证据,支持形态发生性BMP梯度在BMP信号传导后期阶段建立中胚层命运过程中的作用。