Abu-Elmagd Muhammad, Mulvaney Joanna, Wheeler Grant N
Center of Excellence in Genomic Medicine Research, King Abdulaziz University, P.O. Box 80216 Jeddah 21589, Kingdom of Saudi Arabia.
School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
Biol Open. 2017 Dec 15;6(12):1861-1868. doi: 10.1242/bio.026963.
Wnt signalling regulates cardiogenesis during specification of heart tissue and the morphogenetic movements necessary to form the linear heart. Wnt11-mediated non-canonical signalling promotes early cardiac development whilst Wnt11-R, which is expressed later, also signals through the non-canonical pathway to promote heart development. It is unclear which Frizzled proteins mediate these interactions. Frizzled-7 () is expressed during gastrulation in the mesodermal cells fated to become heart, and then in the primary heart field. This expression is complementary to the expression of and We further show co-localisation of with other early- and late-heart-specific markers using double hybridisation. We have used loss of function analysis to determine the role of during heart development. Morpholino antisense oligonucleotide-mediated knockdown of Fzd7 results in effects on heart development, similar to that caused by Wnt11 loss of function. Surprisingly, overexpression of dominant-negative Fzd7 cysteine rich domain (Fzd7 CRD) results in a cardia bifida phenotype, similar to the loss of phenotype. Overexpression of Fzd7 and activation of non-canonical wnt signalling can rescue the effect of Fzd7 CRD. We propose that Fzd7 has an important role during heart development.
Wnt信号通路在心脏组织特化以及形成线性心脏所需的形态发生运动过程中调节心脏发生。Wnt11介导的非经典信号通路促进早期心脏发育,而稍后表达的Wnt11-R也通过非经典途径发出信号以促进心脏发育。目前尚不清楚哪些卷曲蛋白介导这些相互作用。卷曲蛋白-7()在原肠胚形成期间在注定要形成心脏的中胚层细胞中表达,然后在初级心脏区域表达。这种表达与和的表达互补。我们进一步使用双重杂交显示与其他早期和晚期心脏特异性标记物共定位。我们使用功能丧失分析来确定在心脏发育过程中的作用。吗啉代反义寡核苷酸介导的Fzd7敲低导致对心脏发育的影响,类似于Wnt11功能丧失所引起的影响。令人惊讶的是,显性负性Fzd7富含半胱氨酸结构域(Fzd7 CRD)的过表达导致心脏双裂表型,类似于缺失表型。Fzd7的过表达和非经典wnt信号通路的激活可以挽救Fzd7 CRD的作用。我们提出Fzd7在心脏发育过程中具有重要作用。