（封面圖片：古希臘詩(shī)人阿爾基洛科斯（Archilochos）說(shuō)過(guò)“狐貍有很多計(jì)謀,，但是刺猬只有一個(gè),，但那一個(gè)是最好的一個(gè)。”而Michael Ayrton的圖畫很好的反映了這一思想,。它捕捉到了發(fā)育中脊髓運(yùn)動(dòng)神經(jīng)分化機(jī)制中的關(guān)鍵因素,。“刺猬”的一個(gè)計(jì)謀即是確定沿背腹軸的運(yùn)動(dòng)神經(jīng)種類，而“狐貍”的多種計(jì)謀則是控制21個(gè)Hox基因的活動(dòng),。Dasen等的文章揭示了轉(zhuǎn)錄因子FoxP1作為Hox蛋白輔助因子在脊髓運(yùn)動(dòng)神經(jīng)元分化方面所起到的作用,。）
運(yùn)動(dòng)行為的多樣性依賴于在數(shù)以百計(jì)的骨骼肌群中，選擇激活少數(shù)合適骨骼肌的能力,，運(yùn)動(dòng)神經(jīng)元在這其中起著核心作用,。每一塊肌肉都受到一組運(yùn)動(dòng)神經(jīng)元的支配，很多脊髓信號(hào)都用于激活運(yùn)動(dòng)神經(jīng)元,，以實(shí)現(xiàn)運(yùn)動(dòng)的需要,。但是執(zhí)行上述運(yùn)動(dòng)程序的這些神經(jīng)元形成一個(gè)功能回路的機(jī)制一直是個(gè)謎。
在脊髓發(fā)育過(guò)程中,，運(yùn)動(dòng)神經(jīng)元形成分離的柱結(jié)構(gòu),，每個(gè)運(yùn)動(dòng)柱支配一個(gè)不同的外周區(qū)域。其中正中運(yùn)動(dòng)柱（median motor column MMC）神經(jīng)元支配中軸肌,，軸下運(yùn)動(dòng)柱（hypaxial motor column HMC）神經(jīng)元支配體壁肌肉,，節(jié)前運(yùn)動(dòng)柱（preganglionic motor column PGC）神經(jīng)元支配交感神經(jīng)節(jié)，外側(cè)運(yùn)動(dòng)柱（lateral motor column LMC）則支配肢體的肌肉,。由于這些運(yùn)動(dòng)柱的存在,，運(yùn)動(dòng)神經(jīng)元可以很好的控制目標(biāo)肌肉。
決定目標(biāo)肌肉由哪一個(gè)運(yùn)動(dòng)神經(jīng)元支配取決于Hox轉(zhuǎn)錄因子調(diào)節(jié)網(wǎng)絡(luò),。在2008年7月25日的《細(xì)胞》（Cell）上，來(lái)自美國(guó)的Dasen等科學(xué)家發(fā)表文章稱,，他們發(fā)現(xiàn)一種轉(zhuǎn)錄因子FoxP1作為Hox輔助因子,，能對(duì)各個(gè)運(yùn)動(dòng)神經(jīng)元種類進(jìn)行調(diào)節(jié)。
在研究中,，科學(xué)家主要分析了輔助因子的作用,，特別是調(diào)節(jié)脊髓運(yùn)動(dòng)神經(jīng)元分化Hox依賴程序的FoxP蛋白。其中FoxP1是和心臟,、血液發(fā)育相關(guān)的轉(zhuǎn)錄因子,，研究人員證實(shí)它控制整個(gè)脊髓運(yùn)動(dòng)神經(jīng)元多樣性和連結(jié)性的Hox程序的信息輸出,。FoxP1在Hox敏感型運(yùn)動(dòng)柱中表達(dá)，使FoxP1失活能消除運(yùn)動(dòng)神經(jīng)元Hox網(wǎng)絡(luò)的信息輸出,，并將脊髓運(yùn)動(dòng)系統(tǒng)回復(fù)到原始狀態(tài),。而FoxP1的減少同樣改變運(yùn)動(dòng)神經(jīng)元連結(jié)性模式，在這種情況下,，肢體運(yùn)動(dòng)神經(jīng)似乎會(huì)隨機(jī)選擇目標(biāo)肌肉和作用路徑,。單個(gè)的FoxP1轉(zhuǎn)錄因子能以Hox輔助因子的形式整合各種神經(jīng)元種類的連結(jié)性，此外,，科學(xué)家們還表示,，他們的以上發(fā)現(xiàn)證明FoxP1是決定運(yùn)動(dòng)神經(jīng)元多樣性和連結(jié)性的關(guān)鍵因素。（生物谷Bioon.com）
生物谷推薦原始出處：
Cell,，Vol 134, 304-316, 25 July 2008,，Jeremy S. Dasen, Thomas M. Jessell
Hox Repertoires for Motor Neuron Diversity and Connectivity Gated by a Single Accessory Factor, FoxP1
Jeremy S. Dasen,1,3, Alessandro De Camilli,1 Bin Wang,2 Philip W. Tucker,2 and Thomas M. Jessell3,
1 Smilow Neuroscience Program, Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016, USA
2 Department of Molecular Genetics and Microbiology, The University of Texas at Austin, Austin TX 78712, USA
3 Howard Hughes Medical Institute, Kavli Institute for Brain Science, Departments of Neuroscience, and Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA
Corresponding author
Jeremy S. Dasen
[email protected]
Corresponding author
Thomas M. Jessell
[email protected]
Summary
The precision with which motor neurons innervate target muscles depends on a regulatory network of Hox transcription factors that translates neuronal identity into patterns of connectivity. We show that a single transcription factor, FoxP1, coordinates motor neuron subtype identity and connectivity through its activity as a Hox accessory factor. FoxP1 is expressed in Hox-sensitive motor columns and acts as a dose-dependent determinant of columnar fate. Inactivation of Foxp1 abolishes the output of the motor neuron Hox network, reverting the spinal motor system to an ancestral state. The loss of FoxP1 also changes the pattern of motor neuron connectivity, and in the limb motor axons appear to select their trajectories and muscle targets at random. Our findings show that FoxP1 is a crucial determinant of motor neuron diversification and connectivity, and clarify how this Hox regulatory network controls the formation of a topographic neural map.
