科學(xué)家們發(fā)現(xiàn)了一個(gè)在發(fā)育最初階段發(fā)揮關(guān)鍵作用的基因家族,，在此階段,，胚胎已可辨別身體的左右側(cè)，并開始確定器官在體內(nèi)的安放位置,。在小鼠身上的此項(xiàng)發(fā)現(xiàn)能使人們更好地理解人類的某些先天缺陷是如何發(fā)生的,。此項(xiàng)研究成果發(fā)表在1月24日出版的《自然·細(xì)胞生物學(xué)》雜志網(wǎng)絡(luò)版上。
此項(xiàng)研究建立在左右對(duì)稱破缺的胚胎發(fā)育機(jī)理之上,。日本大阪大學(xué)遺傳學(xué)家濱田宏博士及其同事的研究指出,，位于胚胎節(jié)點(diǎn)區(qū)域內(nèi)的細(xì)胞表面的纖毛會(huì)在胚胎外形成左向流動(dòng),，反過來(lái)讓胚胎知道哪邊是左邊。其原因是纖毛朝向節(jié)點(diǎn)細(xì)胞的背部,，且向胚胎尾部?jī)A斜,。
這個(gè)獨(dú)特的位置，與纖毛的順時(shí)針運(yùn)動(dòng)相結(jié)合形成了左向流動(dòng),，隨之胚胎的左右對(duì)稱被打破。據(jù)研究,，如果沒有定向流動(dòng)的建立,，生物體就會(huì)在身體錯(cuò)誤的一側(cè)發(fā)育出器官，從而降低其存活幾率,。
了解了節(jié)點(diǎn)上的纖毛位置與胚胎發(fā)育階段之間的重要關(guān)系后,，研究人員決定進(jìn)一步觀察一個(gè)稱為“散亂”的基因家族是否可引導(dǎo)纖毛遷移至節(jié)點(diǎn)細(xì)胞的背部。在對(duì)“散亂”基因家族的多年研究中,，研究人員通過分別關(guān)閉3個(gè)“散亂”基因中的一個(gè)來(lái)開發(fā)小鼠模型,，以此研究其各自的功能。最終,，研究人員發(fā)現(xiàn),，“散亂”基因可激活平面細(xì)胞極性通路，這個(gè)通路有助于決定細(xì)胞和組織內(nèi)的位置信息,。
論文第一作者,、濱田宏實(shí)驗(yàn)室的研究生橋本正和通過一臺(tái)與顯微鏡相連的高速攝像機(jī)，對(duì)成活小鼠胚胎中的纖毛運(yùn)動(dòng)進(jìn)行了監(jiān)測(cè),，并觀察到了纖毛的位置確實(shí)隨著發(fā)育進(jìn)程而改變,。在左右對(duì)稱破缺發(fā)生前的最早發(fā)育階段，纖毛位于節(jié)點(diǎn)細(xì)胞的中央,，隨著發(fā)育的進(jìn)展,，纖毛逐漸轉(zhuǎn)移到細(xì)胞的背部。
研究人員對(duì)正常小鼠胚胎中的纖毛和帶有“散亂”基因突變胚胎中的纖毛進(jìn)行了比較,。他們發(fā)現(xiàn),，帶有基因突變胚胎中的纖毛位于節(jié)點(diǎn)細(xì)胞的非正常位置，從而無(wú)法形成左向流動(dòng),。
研究人員表示,，此一發(fā)現(xiàn)提供了人類發(fā)育的最基本層次的信息，即人類究竟是如何產(chǎn)生左右差別的,，最終這種差異又如何導(dǎo)致了心臟生長(zhǎng)在左邊,，而肝臟生長(zhǎng)在右邊。對(duì)胚胎發(fā)育進(jìn)程的清晰了解將有助于更好地理解人類先天缺陷的成因,，并找到設(shè)法糾正這些缺陷的方法,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Cell Biology 12, 170 - 176 (2010) 24 January 2010 | doi:10.1038/ncb2020
Planar polarization of node cells determines the rotational axis of node cilia
Masakazu Hashimoto1, Kyosuke Shinohara1, Jianbo Wang2,7, Shingo Ikeuchi1, Satoko Yoshiba1, Chikara Meno1,8, Shigenori Nonaka3, Shinji Takada4, Kohei Hatta5, Anthony Wynshaw-Boris2,6 & Hiroshi Hamada1
Rotational movement of the node cilia generates a leftward fluid flow in the mouse embryo1 because the cilia are posteriorly tilted2, 3. However, it is not known how anterior-posterior information is translated into the posterior tilt of the node cilia. Here, we show that the basal body of node cilia is initially positioned centrally but then gradually shifts toward the posterior side of the node cells. Positioning of the basal body and unidirectional flow were found to be impaired in compound mutant mice lacking Dvl genes. Whereas the basal body was normally positioned in the node cells of Wnt3a?/? embryos, inhibition of Rac1, a component of the noncanonical Wnt signalling pathway, impaired the polarized localization of the basal body in wild-type embryos. Dvl2 and Dvl3 proteins were found to be localized to the apical side of the node cells, and their location was polarized to the posterior side of the cells before the posterior positioning of the basal body. These results suggest that posterior positioning of the basal body, which provides the posterior tilt to node cilia, is determined by planar polarization mediated by noncanonical Wnt signalling.
1 Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University and CREST, Japan Science and Technology Corporation (JST), 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
2 Department of Pediatrics and Medicine, University of California, San Diego, 9500 Gilman Drive, MC 0627, La Jolla, CA 92093-0627, USA.
3 Developmental Biology Section, National Institute for Basic Biology, Nishigonaka 38, Myodaiji, Okazaki 444-8585, Aichi, Japan.
4 Okazaki Institute for Integrative Biosciences, National Institutes of Natural Sciences, 5-1 Higashiyama, Okazaki, Aichi 444-8787, Japan.
5 Graduate School of Life Science, University of Hyogo, 3-2-1 Kouto, Kamigori, Ako-gun, Hyogo 678-1297, Japan.
6 Department of Pediatrics and Institute for Human Genetics, University of California San Francisco School of Medicine, San Francisco, CA 94143-0794, USA.
7 Current address: Department of Cell Biology, School of Medicine, University of Alabama, Birmingham, 1530 3rd Ave. South, Birmingham, AL 35294, USA.
8 Current address: Department of Developmental Biology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
