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[交流] 【轉(zhuǎn)帖】單基因調(diào)控脊髓中的運(yùn)動(dòng)神經(jīng)元

單基因調(diào)控脊髓中的運(yùn)動(dòng)神經(jīng)元

《每日科學(xué)》2010年9月12日?qǐng)?bào)道 ——發(fā)表于2010年9月9日的《Neuron》（《神經(jīng)元》）的這項(xiàng)發(fā)現(xiàn)確實(shí)令人驚訝與始料未及：紐約大學(xué)朗格尼醫(yī)學(xué)中心的科學(xué)家發(fā)現(xiàn)一種單基因型是脊髓中運(yùn)動(dòng)神經(jīng)元的主要組織者，可能有助于科學(xué)家開發(fā)針對(duì)脊髓側(cè)索硬化癥或脊髓損傷的新療法。

該“主要組織者”是Hox基因家族的一名成員。Hox基因家族以控制身體發(fā)育的總體模式著稱。通過協(xié)調(diào)早期胚胎一系列基因表達(dá)，Hox基因總攬動(dòng)物的總體結(jié)構(gòu)的創(chuàng)建與軀體局部導(dǎo)向。科學(xué)家在果蠅中首次發(fā)現(xiàn)這些基因。從那時(shí)起，他們?cè)诓溉閯?dòng)物中檢測(cè)Hox（基因家族）活動(dòng)。人類有39個(gè)這種基因，并且其中21個(gè)已被證實(shí)起著協(xié)調(diào)脊髓運(yùn)動(dòng)神經(jīng)元的作用。

紐約大學(xué)朗格尼醫(yī)學(xué)中心生理學(xué)與神經(jīng)科學(xué)系副教授杰里米•戴森（Jeremy S. Dasen）博士說：“我們知道有21個(gè)Hox基因決定了脊髓運(yùn)動(dòng)神經(jīng)元與肢體肌肉之間的連接方式。但是在本研究中讓我們驚訝的是，單一Hox基因發(fā)揮了運(yùn)動(dòng)神經(jīng)元及其連接的全局指揮者的中心角色作用。下一步將是觀察神經(jīng)元中的Hoxc9影響諸如行走與呼吸等運(yùn)動(dòng)行為的具體過程�！�

哺乳動(dòng)物需要大量的運(yùn)動(dòng)神經(jīng)元來控制各種各樣的用于協(xié)調(diào)運(yùn)動(dòng)的肌細(xì)胞。合適的功能取決于在胚胎階段這些神經(jīng)元中的每一個(gè)是否能夠在脊髓與需要控制的肌群之間找到自己的（發(fā)育）路徑。杰里米•戴森博士及其同事一直在努力發(fā)現(xiàn)這種運(yùn)動(dòng)神經(jīng)元多樣性的藍(lán)圖。

為了完成這一研究任務(wù)，科學(xué)家們研究了Hoxc9基因中攜帶一種突變的小鼠。他們分析了區(qū)分肢體運(yùn)動(dòng)神經(jīng)元與胸部區(qū)域運(yùn)動(dòng)神經(jīng)元的分子標(biāo)記物，發(fā)現(xiàn)Hoxc9的突變使胸部區(qū)域運(yùn)動(dòng)神經(jīng)元搖身一變，成了肢體運(yùn)動(dòng)神經(jīng)元。在一系列的生物化學(xué)實(shí)驗(yàn)中，他們進(jìn)一步顯示了Hoxc9通過抑制致力于肢體（運(yùn)動(dòng)）協(xié)調(diào)的Hox基因來精密統(tǒng)籌運(yùn)動(dòng)神經(jīng)元的基因表達(dá)。杰里米•戴森博士補(bǔ)充說：“目前我們正在嘗試?yán)斫獾氖牵荷窠?jīng)系統(tǒng)具體上是如何連接才得以成功控制諸如呼吸與行走呢？我們也正在同時(shí)觀察遺傳程序能夠進(jìn)一步控制這些神經(jīng)回路的具體過程；通過探索這種（神經(jīng)連接）范式，我們將為自己深入觀察生物體內(nèi)的至關(guān)重要的（神經(jīng)）回路輔平道路�！�

本論文的共同作者有：Heekyung Jung、朱利•拉康伯（Julie Lacombe）以及紐約大學(xué)朗格尼醫(yī)學(xué)中心的喬納森•格林司坦（Jonathan Grinstein）。本研究在哥倫比亞大學(xué)醫(yī)學(xué)中心、麻薩諸塞州理工大學(xué)與美國Memorial Sloan Kettering 癌癥中心（該中心是世界上歷史最悠久的和最大的私人癌癥中心 —— 譯者）的研究者們合作下共同完成。

本研究得到美國馬里蘭州貝塞斯達(dá)國立衛(wèi)生研究院的資金支持。

參考文獻(xiàn)：

Heekyung Jung, Julie Lacombe, Esteban O. Mazzoni, Karel F. Liem, Jonathan Grinstein, Shaun Mahony, Debnath Mukhopadhyay, David K. Gifford, Richard A. Young, Kathryn V. Anderson et al. Global Control of Motor Neuron Topography Mediated by the Repressive Actions of a Single Hox Gene. Neuron, 67(5) pp. 781 - 796 DOI: 10.1016/j.neuron.2010.08.008

Single Gene Regulates Motor Neurons in Spinal Cord

ScienceDaily (Sep. 12, 2010) — In a surprising and unexpected discovery, scientists at NYU Langone Medical Center have found that a single type of gene acts as a master organizer of motor neurons in the spinal cord. The finding, published in the September 9, 2010 issue of Neuron, could help scientists develop new treatments for diseases such as Lou Gehrig's disease or spinal cord injury.

The "master organizer" is a member of the Hox family of genes, best known for controlling the overall pattern of body development. By orchestrating a cascade of gene expression in the early embryo, Hox genes allow for the creation of an animal's overall structure and body part orientation. Scientists first discovered the genes in fruit flies but they have since detected Hox activity in mammals. Humans harbor 39 such genes and 21 have been identified as coordinating motor neurons in the spinal cord.

"We knew that there were 21 Hox genes that determine how connections are made between motor neurons in the spinal cord and muscles in the limbs," says Jeremy S. Dasen, PhD, an associate professor in the Departments of Physiology and Neuroscience at NYU Langone Medical Center and a Howard Hughes Medical Institute Early Career Scientist. "But what was surprising to us in this study was that a single Hox gene acts as a global organizer of motor neurons and their connections. The next step will be to see how Hoxc9 in motor neurons affect motor behaviors such as walking and breathing."

In mammals, many hundreds of motor neurons are needed to control the variety of muscle cells used to coordinate movement. Proper function depends on each of these neurons in the embryo finding its way from the spinal cord to the group of muscles that it is equipped to control. Dr. Dasen and his colleagues have been working to discover the blueprint for this motor neuron diversity.

For this study, scientists studied mice with a mutation in Hoxc9 gene. They analyzed the molecular markers that distinguished between motor neurons in the limb and thoracic area and discovered mutation of Hoxc9 transformed the thoracic motor neurons into limb motor neurons. In a series of biochemical experiments they further showed that Hoxc9 orchestrates gene expression in motor neurons by repressing the Hox genes dedicated to limb coordination.

"What we are trying to understand is how the nervous system is wired to control movements such as breathing and walking and see how genetic programs can further control these circuits in terms of exploring this paradigm as a way at looking at the vital circuits of the body," adds Dr. Dasen.

Co-authors of the study include Heekyung Jung, Julie Lacombe, and Jonathan Grinstein of NYU Langone Medical Center. The research was done in collaboration with researchers at Columbia University Medical Center, Massachusetts Institute of Technology and Memorial Sloan Kettering Cancer Center.

The study was supported by a grant from the National Institutes of Health in Bethesda, Maryland.

原文下載：http://u.115.com/file/f7b5152bc7
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