?加州大學(xué)圣迭戈分校（UCSD）生物學(xué)家發(fā)現(xiàn)，和流行的學(xué)說(shuō)不同，果蠅和人類(lèi)等脊椎動(dòng)物早期的神經(jīng)系統(tǒng)形成過(guò)程由同樣的祖先保留下來(lái),。
??在9月12號(hào)的《Public Library of Science Biology》上,，研究者報(bào)道了在果蠅和小雞胚胎中,，都有一種叫做BMP的蛋白質(zhì),，它能使早期胚胎中的某些基因被表達(dá)或被關(guān)閉，從而使胚胎細(xì)胞分化為中樞神經(jīng)系統(tǒng)中的三類(lèi)主要部分,。這一結(jié)果揭示了早期神經(jīng)系統(tǒng)發(fā)育具有統(tǒng)一的模式,，至少在神經(jīng)形成的機(jī)制上。這一機(jī)制由5億年前的祖先保留下來(lái),。
??UCSD生物學(xué)教授Ethan Bier說(shuō)：“這是我們找到的第一個(gè)證據(jù),，證明BMP在建立脊椎和無(wú)脊椎動(dòng)物沿腹-背軸的神經(jīng)系統(tǒng)基因表達(dá)模式上的普遍作用,。結(jié)果表明這一過(guò)程是由共同祖先保留下來(lái)的，而非普遍接受的由各自獨(dú)立進(jìn)化而來(lái),。”
??在復(fù)雜生物體形成的早期,，胚胎只是一個(gè)相同細(xì)胞組成的小球。在其中BMP將胚胎分化為神經(jīng)組織和非神經(jīng)組織,。在這一神經(jīng)誘導(dǎo)過(guò)程中，BMP含量高的區(qū)域神經(jīng)系統(tǒng)的形成被抑制,。
??不過(guò),，關(guān)于BMP是否在神經(jīng)組織進(jìn)一步分化為3部分的過(guò)程中發(fā)揮作用，學(xué)者還不是很清楚,。雖然神經(jīng)特征基因的表達(dá)與BMP有關(guān),，但人們推斷在果蠅和脊椎動(dòng)物中存在不同的機(jī)制。比如,，脊椎動(dòng)物存在Hedgehog蛋白,，它是這一過(guò)程的關(guān)鍵因素。而在果蠅中存在相應(yīng)的蛋白質(zhì)Dorsal,。
??文章第一作者,，UCSD生物學(xué)博士后Mieko Mizutani說(shuō)：“由于Dorsal的統(tǒng)治性作用，我們很難直接測(cè)試BMP在果蠅神經(jīng)組織形成中的角色,。去掉Dorsal會(huì)造成胚胎里根本沒(méi)有神經(jīng)組織,。所以我們從基因?qū)W上重建了胚胎，使得內(nèi)部Dorsal含量一致,。然后就可以研究BMP對(duì)神經(jīng)組織分化的影響了,。我們花了約4年的時(shí)間建立這種方法，它也能被用于將來(lái)研究其它基因表達(dá)或關(guān)閉的機(jī)理,。”
??通過(guò)使用Bier和小組在兩年前發(fā)展起來(lái)的“多元標(biāo)記”方法,，Mizutani可以用不同顏色的熒光分子探測(cè)哪些神經(jīng)特征基因會(huì)受到BMP的影響。結(jié)果證明,，BMP在神經(jīng)分化中的作用和在早期神經(jīng)誘導(dǎo)過(guò)程的一樣,，主要用于關(guān)閉神經(jīng)特征基因。這過(guò)程主要受BMP濃度的影響,。
??果蠅的結(jié)果促使作者思考同樣過(guò)程是否也發(fā)生在脊椎動(dòng)物中,。他們找到華盛頓大學(xué)生物學(xué)教授Henk Roelink以及他的研究生Neva Meyer作為合作者。小組在小雞晶胚上作了類(lèi)似實(shí)驗(yàn),。
??Roelink在放有雞晶胚神經(jīng)組織的培養(yǎng)皿里加入了BMP,。他們也要保證Hedgehog蛋白（對(duì)應(yīng)果蠅中的Dorsal）濃度一致。結(jié)果小雞的神經(jīng)特征基因也受到BMP的影響,，和果蠅一樣,。Bier說(shuō)：“結(jié)果表明,，遠(yuǎn)古祖先的BMP蛋白足夠使它們形成整個(gè)腹-背軸。BMP和神經(jīng)特征基因似乎是由共同祖先保留下來(lái)的,，而Dorsal和Hedgehog這類(lèi)蛋白質(zhì)更像是分化為脊椎和無(wú)脊椎動(dòng)物后分別產(chǎn)生的,。而隨著大型生物的進(jìn)化，單一的蛋白質(zhì)已經(jīng)不足以細(xì)分各個(gè)組織了,。”
英文原文：
? Mechanism to Organize Nervous System Conserved in Evolution
A study led by University of California, San Diego biologists suggests that, contrary to the prevailing view, the process in early development that partitions the nervous system in fruit flies and vertebrates, like humans, evolved from a common ancestor.
In the September 12 issue of the journal Public Library of Science Biology, the researchers report that in both fruit fly and chick embryos proteins called BMPs play similar roles in telling cells in the early embryo to switch certain genes on and off, specifying the identity of the cells making up the three primary subdivisions of the central nervous system. The findings suggest a unified model of early neural development in which at least part of the mechanism for creating neural patterning has been preserved from a shared ancestral organism that lived over 500 million years ago.
Fruit fly embryo with colors indicating a localized perturbation in the activation
of three genes that determine neural identities.
Credit: Mieko Mizutani, UCSD
Click image for larger version.
“We have provided the first evidence for a common role of BMPs in establishing the pattern of gene expression along the dorsal-ventral axis of the nervous system of vertebrates and invertebrates,” said Ethan Bier, a professor of biology at UCSD and senior author on the study. “Our results suggest that this process has been conserved from a common ancestor rather than evolving separately as had been previously believed.”
Early in the development of a complex organism, when it is a ball of indistinguishable cells, BMP gradients are responsible for partitioning embryos into neural and non-neural tissue. During this phase, often referred to as neural induction, high levels of BMPs in non-neural regions actively suppress neural development. This role of BMPs is one of the best examples of a conserved evolutionary process.
However, it has been less clear whether BMPs also play a common role in further subdividing the nerve tissue into three distinct regions. Although the so-called neural identity genes get switched on in a similar pattern in relation to the BMP source, it has been speculated that distinct mechanisms operate to determine those activation patterns in fruit flies versus vertebrates. For example, in vertebrates a protein called Hedgehog is a key patterning agent in this process, while in flies a gradient of a different protein called Dorsal plays a comparable role.
“Because of the dominant role of the gradient of Dorsal protein, it has not been possible to directly test the role of BMPs in patterning nerve tissue in fruit flies.” explained Mieko Mizutani, a postdoctoral researcher in biology at UCSD and the lead author on the paper. “Eliminating Dorsal results in embryos that do not have any nerve tissue. Therefore, we had to genetically reconstruct embryos that had a uniform concentration of Dorsal throughout. Then we could examine how neural patterning was affected by a BMP gradient. The techniques took approximately fours years to develop and will also be useful for future research to understand how the many genes of the genome are turned on or off in groups.”
In these embryos with a uniform concentration of Dorsal, the researchers switched on the gene for the fruit fly BMP in a narrow stripe. Using a technique called multiplex labeling that Bier, Mizutani and fellow UCSD biologists developed two years ago, Mizutani was able to use different colored fluorescent molecules to determine which neural identity genes were activated in response to the BMP gradient. She determined that BMPs acted the same way as they do earlier during neural induction, namely to shut off neural identity genes. Because BMPs can shut some neural genes off better than others, the pattern in which the neural identity genes get switched off depends on the concentration of BMP.
The finding that a BMP gradient controlled neural development in fruit flies prompted the authors to ask whether the same might be true in vertebrates. Bier and Mizutani collaborated with Henk Roelink, a professor of biology at the University of Washington, Seattle and his graduate student Néva Meyer. They performed analogous experiments on chick embryos.
Roelink and Meyer added doses of BMP to a Petri plate containing nerve tissue from early chick embryos. As with fruit flies, they had to hold constant the concentration of another protein involved in dorsal-ventral patterning (in this case Hedgehog rather than Dorsal). The neural identity genes in chick responded to the BMP gradient just as their counterparts responded in fruit flies. “Our findings suggest that BMPs may once have been sufficient to organize the entire dorsal-ventral axis of a common ancestor,” concluded Bier.
“BMPs and the neural identity genes appear to have been conserved in evolution, while other cues such as Dorsal in flies and Hedgehog in vertebrates may have been borrowed from other pattern systems after the split between vertebrate and invertebrate lineages. As larger organisms evolved, the gradient of a single protein may not have been able to provide sufficient information to subdivide the embryo from top to bottom.”
