Sox5 controls dorsal progenitor and interneuron specification in the spinal cord
Sox5 controls dorsal progenitor and interneuron specification in the spinal cord
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Sox5 控制脊髓中的背侧祖细胞和中间神经元规范
DOI：
10.1002/dneu.22240
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发表时间：
2014
影响因子：
3
通讯作者：
Morales AV.
中科院分区：
文献类型：
--
作者：
Quiroga A.C;Stolt C.C;Diez del Corral R;Dimitrov S;Pérez-Alcalá S;Sock E;Barbas J.A;Wegner M. ;Morales AV.
脊髓中躯体感觉回路的基本组织在背神经管的初始模式形成期间已经建立。外部信号，如Wnt和TGF-β途径，激活转录因子的组合密码，这些转录因子负责产生背侧祖细胞（dp）的离散结构域模式。这些祖细胞将产生不同的背侧中间神经元（dI）。Wnt/β catenin信号通路控制dp/dI1 - 3祖细胞和中间神经元的特化。根据该领域的当前模型，Wnt/β连环蛋白活性似乎以分级的方式在脊髓中起作用，因为不同的相对水平决定了相邻祖细胞的身份。然而，目前尚不清楚这种活性梯度是如何控制的，以及dI1 - 3的身份是如何通过Wnt信号传导进行差异调节的。我们已经确定，两个SoxD转录因子，Sox5和Sox6，在神经管中的背侧祖细胞的限制性结构域中表达。在鸡胚胎中使用获得和丧失功能的方法，我们已经确定Sox 5控制着dp2和dp3祖细胞的细胞命运特化，因此，控制着相应的背侧中间神经元（dI2和dI3）的正确数量。此外，Sox 5通过直接转录诱导负Wnt通路调节因子Axin 2来限制背侧Wnt信号传导活性来发挥其功能。通过这种方式，Sox 5作为Wnt通路调节剂，有助于锐化Wnt/β连环蛋白活性的背侧梯度，以控制参与躯体感觉中继的两种功能不同类型的中间神经元dI2和dI3的区别。© 2014 Wiley Periodicals，Inc.开发神经生物学75：522 - 538，2015年
The basic organization of somatosensory circuits in the spinal cord is already setup during the initial patterning of the dorsal neural tube. Extrinsic signals, such as Wnt and TGF‐β pathways, activate combinatorial codes of transcription factors that are responsible for generating a pattern of discrete domains of dorsal progenitors (dp). These progenitors will give rise to distinct dorsal interneurons (dI). The Wnt/ βcatenin signaling pathway controls specification of dp/dI1–3 progenitors and interneurons. According to the current model in the field, Wnt/βcatenin activity seems to act in a graded fashion in the spinal cord, as different relative levels determine the identity of adjacent progenitors. However, it is not clear how this activity gradient is controlled and how the identities of dI1–3 are differentially regulated by Wnt signalling. We have determined that two SoxD transcription factors, Sox5 and Sox6, are expressed in restricted domains of dorsal progenitors in the neural tube. Using gain‐ and loss‐of function approaches in chicken embryos, we have established that Sox5 controls cell fate specification of dp2 and dp3 progenitors and, as a result, controls the correct number of the corresponding dorsal interneurons (dI2 and dI3). Furthermore, Sox5 exerts its function by restricting dorsally Wnt signaling activity via direct transcriptional induction of the negative Wnt pathway regulatorAxin2. By that way, Sox5 acts as a Wnt pathway modulator that contributes to sharpen the dorsal gradient of Wnt/βcatenin activity to control the distinction of two functionally distinct types of interneurons, dI2 and dI3 involved in the somatosensory relay. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 522–538, 2015
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