William Christopher M, Tanabe Yasuto, Jessell Thomas M
Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Center for Neurobiology and Behavior, Columbia University, 701 West 168 Street, New York, NY 10032, USA.
Development. 2003 Apr;130(8):1523-36. doi: 10.1242/dev.00358.
In the developing spinal cord, motor neurons acquire columnar subtype identities that can be recognized by distinct profiles of homeodomain transcription factor expression. The mechanisms that direct the differentiation of motor neuron columnar subtype from an apparently uniform group of motor neuron progenitors remain poorly defined. In the chick embryo, the Mnx class homeodomain protein MNR2 is expressed selectively by motor neuron progenitors, and has been implicated in the specification of motor neuron fate. We show here that MNR2 expression persists in postmitotic motor neurons that populate the median motor column (MMC), whereas its expression is rapidly extinguished from lateral motor column (LMC) neurons and from preganglionic autonomic neurons of the Column of Terni (CT). The extinction of expression of MNR2, and the related Mnx protein HB9, from postmitotic motor neurons appears to be required for the generation of CT neurons but not for LMC generation. In addition, MNR2 and HB9 are likely to mediate the suppression of CT neuron generation that is induced by the LIM HD protein Lim3. Finally, MNR2 appears to regulate motor neuron identity by acting as a transcriptional repressor, providing further evidence for the key role of transcriptional repression in motor neuron specification.
在发育中的脊髓中，运动神经元获得柱状亚型身份，这可通过同源结构域转录因子表达的不同特征来识别。将运动神经元柱状亚型从明显均一的运动神经元祖细胞群中分化出来的机制仍不清楚。在鸡胚中，Mnx类同源结构域蛋白MNR2由运动神经元祖细胞选择性表达，并与运动神经元命运的特化有关。我们在此表明，MNR2表达在构成正中运动柱（MMC）的有丝分裂后运动神经元中持续存在，而其表达在外侧运动柱（LMC）神经元和脊髓中间外侧核（CT）的节前自主神经元中迅速消失。有丝分裂后运动神经元中MNR2及相关Mnx蛋白HB9表达的消失似乎是生成CT神经元所必需的，但不是生成LMC所必需的。此外，MNR2和HB9可能介导由LIM同源结构域蛋白Lim3诱导的对CT神经元生成的抑制。最后，MNR2似乎通过作为转录抑制因子来调节运动神经元身份，为转录抑制在运动神经元特化中的关键作用提供了进一步证据。
