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[交流] 【转帖】单基因调控脊髓中的运动神经元

单基因调控脊髓中的运动神经元

《每日科学》2010年9月12日报道 ——发表于2010年9月9日的《Neuron》（《神经元》）的这项发现确实令人惊讶与始料未及：纽约大学朗格尼医学中心的科学家发现一种单基因型是脊髓中运动神经元的主要组织者，可能有助于科学家开发针对脊髓侧索硬化症或脊髓损伤的新疗法。

该“主要组织者”是Hox基因家族的一名成员。Hox基因家族以控制身体发育的总体模式著称。通过协调早期胚胎一系列基因表达，Hox基因总揽动物的总体结构的创建与躯体局部导向。科学家在果蝇中首次发现这些基因。从那时起，他们在哺乳动物中检测Hox（基因家族）活动。人类有39个这种基因，并且其中21个已被证实起着协调脊髓运动神经元的作用。

纽约大学朗格尼医学中心生理学与神经科学系副教授杰里米•戴森（Jeremy S. Dasen）博士说：“我们知道有21个Hox基因决定了脊髓运动神经元与肢体肌肉之间的连接方式。但是在本研究中让我们惊讶的是，单一Hox基因发挥了运动神经元及其连接的全局指挥者的中心角色作用。下一步将是观察神经元中的Hoxc9影响诸如行走与呼吸等运动行为的具体过程。”

哺乳动物需要大量的运动神经元来控制各种各样的用于协调运动的肌细胞。合适的功能取决于在胚胎阶段这些神经元中的每一个是否能够在脊髓与需要控制的肌群之间找到自己的（发育）路径。杰里米•戴森博士及其同事一直在努力发现这种运动神经元多样性的蓝图。

为了完成这一研究任务，科学家们研究了Hoxc9基因中携带一种突变的小鼠。他们分析了区分肢体运动神经元与胸部区域运动神经元的分子标记物，发现Hoxc9的突变使胸部区域运动神经元摇身一变，成了肢体运动神经元。在一系列的生物化学实验中，他们进一步显示了Hoxc9通过抑制致力于肢体（运动）协调的Hox基因来精密统筹运动神经元的基因表达。杰里米•戴森博士补充说：“目前我们正在尝试理解的是：神经系统具体上是如何连接才得以成功控制诸如呼吸与行走呢？我们也正在同时观察遗传程序能够进一步控制这些神经回路的具体过程；通过探索这种（神经连接）范式，我们将为自己深入观察生物体内的至关重要的（神经）回路辅平道路。”

本论文的共同作者有：Heekyung Jung、朱利•拉康伯（Julie Lacombe）以及纽约大学朗格尼医学中心的乔纳森•格林司坦（Jonathan Grinstein）。本研究在哥伦比亚大学医学中心、麻萨诸塞州理工大学与美国Memorial Sloan Kettering 癌症中心（该中心是世界上历史最悠久的和最大的私人癌症中心 —— 译者）的研究者们合作下共同完成。

本研究得到美国马里兰州贝塞斯达国立卫生研究院的资金支持。

参考文献：

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.

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