近日，國際著名雜志PLoS Biology在線刊登了中科院遺傳與發(fā)育生物學(xué)研究所研究人員的最新研究成果“Maternal xNorrin, a Canonical Wnt Signaling Agonist and TGF-β Antagonist, Controls Early Neuroectoderm Specification in Xenopus,，”,，文章中，研究者發(fā)現(xiàn)了控制早期中樞神經(jīng)系統(tǒng)發(fā)育的關(guān)鍵母源基因,。
啟動脊椎動物中樞神經(jīng)系統(tǒng)發(fā)育是動物發(fā)育進(jìn)程中最重要的過程之一。中樞神經(jīng)系統(tǒng)最早來源于神經(jīng)前體細(xì)胞，因此神經(jīng)前體細(xì)胞的誘導(dǎo)和特化是發(fā)育生物學(xué)最重要的科學(xué)問題之一,。神經(jīng)前體細(xì)胞是在胚胎背-腹軸建立過程中誘導(dǎo)產(chǎn)生的。以前的研究表明,，β–catenin分子在胚胎背-腹軸建立過程中起關(guān)鍵作用,，其激活依賴于母源因子Wnt11。然而,，β-catenin激活并不能完全由Wnt11的活性解釋,，因此尋找特異在背部外胚層中激活β-catenin并啟動神經(jīng)前體細(xì)胞發(fā)育的母源因子就顯得尤其重要。
中科院遺傳與發(fā)育生物學(xué)研究所張建研究組以非洲爪蛙為模式動物,，發(fā)現(xiàn)母源xNorrin分子在早期胚胎發(fā)育中可以激活β-catenin并導(dǎo)致背部外胚層細(xì)胞發(fā)育為神經(jīng)組織,。抑制母源xNorrin活性導(dǎo)致頭部神經(jīng)系統(tǒng)缺失。該研究還發(fā)現(xiàn),，xNorrin可通過不依賴于Wnt信號通路直接抑制BMP/Nodal信號傳遞,。
該結(jié)果為從一個新的角度解釋人類因Norrin基因缺陷而導(dǎo)致Norrie綜合癥的致病機(jī)制提供了線索。
張建研究組博士研究生徐素宏為第一作者,，該研究與清華大學(xué)吳畏教授實驗室合作完成,，得到了中科院、科技部和國家自然科學(xué)基金委的資助,。（生物谷Bioon.com）
doi:10.1371/journal.pbio.1001286
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Maternal xNorrin, a Canonical Wnt Signaling Agonist and TGF-β Antagonist, Controls Early Neuroectoderm Specification in Xenopus
Suhong Xu1,2¤, Feng Cheng1,2, Juan Liang3, Wei Wu3, Jian Zhang1*
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.
