导读：国际著名杂志PLoS Biology在线刊登了中科院张建等的研究成果，文章中，研究人员发现了控制早期中枢神经系统发育的关键母源基因。该结果为从一个新的角度解释人类因Norrin基因缺陷而导致Norrie综合症的致病机制提供了线索。
近日，国际著名杂志PLoS Biology在线刊登了中科院遗传与发育生物学研究所研究人员张建等的最新研究成果“Maternal xNorrin, a Canonical Wnt Signaling Agonist and TGF-β Antagonist, Controls Early Neuroectoderm Specification in Xenopus，”，文章中，研究者发现了控制早期中枢神经系统发育的关键母源基因。
启动脊椎动物中枢神经系统发育是动物发育进程中最重要的过程之一。中枢神经系统最早来源于神经前体细胞，因此神经前体细胞的诱导和特化是发育生物学最重要的科学问题之一。神经前体细胞是在胚胎背-腹轴建立过程中诱导产生的。以前的研究表明，β–catenin分子在胚胎背-腹轴建立过程中起关键作用，其激活依赖于母源因子Wnt11。然而，β-catenin激活并不能完全由Wnt11的活性解释，因此寻找特异在背部外胚层中激活β-catenin并启动神经前体细胞发育的母源因子就显得尤其重要。
中科院遗传与发育生物学研究所张建研究组以非洲爪蛙为模式动物，发现母源xNorrin分子在早期胚胎发育中可以激活β-catenin并导致背部外胚层细胞发育为神经组织。抑制母源xNorrin活性导致头部神经系统缺失。该研究还发现，xNorrin可通过不依赖于Wnt信号通路直接抑制BMP/Nodal信号传递。
该结果为从一个新的角度解释人类因Norrin基因缺陷而导致Norrie综合症的致病机制提供了线索。
张建研究组博士研究生徐素宏为第一作者，该研究与清华大学吴畏教授实验室合作完成，得到了中科院、科技部和国家自然科学基金委的资助。
Maternal xNorrin, a Canonical Wnt Signaling Agonist and TGF-β Antagonist, Controls Early Neuroectoderm Specification in Xenopus
Suhong Xu, Feng Cheng, Juan Liang, Wei Wu, Jian Zhang
Dorsal–ventral specification in the amphibian embryo is controlled by β-catenin, whose activation in all dorsal cells is dependent on maternal Wnt11. However, it remains unknown whether other maternally secreted factors contribute to β-catenin activation in the dorsal ectoderm. Here, we show that maternal Xenopus Norrin (xNorrin) promotes anterior neural tissue formation in ventralized embryos. Conversely, when xNorrin function is inhibited, early canonical Wnt signaling in the dorsal ectoderm and the early expression of the zygotic neural inducers Chordin, Noggin, and Xnr3 are severely suppressed, causing the loss of anterior structures. In addition, xNorrin potently inhibits BMP- and Nodal/Activin-related functions through direct binding to the ligands. Moreover, a subset of Norrin mutants identified in humans with Norrie disease retain Wnt activation but show defective inhibition of Nodal/Activin-related signaling in mesoderm induction, suggesting that this disinhibition causes Norrie disease. Thus, xNorrin is an unusual molecule that acts on two major signaling pathways, Wnt and TGF-β, in opposite ways and is essential for early neuroectoderm specification.
文献链接：https://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001286
