Reconstruction of phrenic neuron identity in embryonic stem cell-derived motor neurons.
Reconstruction of phrenic neuron identity in embryonic stem cell-derived motor neurons.
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DOI：
10.1242/dev.097188
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发表时间：
2014-02
期刊：
影响因子：
--
通讯作者：
Lieberam I
中科院分区：
文献类型：
--
作者：
Machado CB;Kanning KC;Kreis P;Stevenson D;Crossley M;Nowak M;Iacovino M;Kyba M;Chambers D;Blanc E;Lieberam I
呼吸空气是生活在陆地上的脊椎动物的基本运动功能。驱动呼吸的节奏在中枢神经系统内产生，并通过脊髓运动神经元的专门子集传递到调节肺容量的肌肉。在哺乳动物中，关键的呼吸肌是膈肌，其由膈核中的运动神经元支配。值得注意的是，对于这种关键的运动神经元亚型是如何在胚胎发育过程中产生的，人们知之甚少。在这里，我们使用直接分化的运动神经元从小鼠胚胎干细胞作为一种工具，以确定基因，指导膈神经元的身份。我们发现，三个决定因素，Pou 3f 1，Hoxa 5和Notch，共同作用，以促进膈神经元的分子身份。我们发现，Notch信号诱导Pou 3f 1在体外和体内发育中的运动神经元。这表明膈神经元谱系是通过颈中段水平的Notch配体的局部来源建立的。此外，我们发现，Pou 3f 1和Hoxa 5调节的钙粘蛋白Pcdh 10和Pou 3f 1控制的Cdh 10都是运动神经元胞体相似聚集的介质。这种特异性的Pcdh 10/Cdh 10活性可能提供了膈神经元组装成一个独特的核的手段。我们的研究提供了一个框架，了解膈神经元身份是如何赋予的，并将有助于直接从多能干细胞产生这种罕见的，难以接近的，但重要的神经元亚型，从而促进后续的功能研究。
Air breathing is an essential motor function for vertebrates living on land. The rhythm that drives breathing is generated within the central nervous system and relayed via specialised subsets of spinal motor neurons to muscles that regulate lung volume. In mammals, a key respiratory muscle is the diaphragm, which is innervated by motor neurons in the phrenic nucleus. Remarkably, relatively little is known about how this crucial subtype of motor neuron is generated during embryogenesis. Here, we used direct differentiation of motor neurons from mouse embryonic stem cells as a tool to identify genes that direct phrenic neuron identity. We find that three determinants, Pou3f1, Hoxa5 and Notch, act in combination to promote a phrenic neuron molecular identity. We show that Notch signalling induces Pou3f1 in developing motor neurons in vitro and in vivo. This suggests that the phrenic neuron lineage is established through a local source of Notch ligand at mid-cervical levels. Furthermore, we find that the cadherins Pcdh10, which is regulated by Pou3f1 and Hoxa5, and Cdh10, which is controlled by Pou3f1, are both mediators of like-like clustering of motor neuron cell bodies. This specific Pcdh10/Cdh10 activity might provide the means by which phrenic neurons are assembled into a distinct nucleus. Our study provides a framework for understanding how phrenic neuron identity is conferred and will help to generate this rare and inaccessible yet vital neuronal subtype directly from pluripotent stem cells, thus facilitating subsequent functional investigations.
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影响因子：
16.2
作者：
Liu, JP;Laufer, E;Jessell, TM
通讯作者：
Jessell, TM
影响因子：
64.5
作者：
Dasen, Jeremy S.;De Camilli, Alessandro;Jessell, Thomas M.
通讯作者：
Jessell, Thomas M.
影响因子：
64.8
作者：
Dasen, JS;Liu, JP;Jessell, TM
通讯作者：
Jessell, TM
影响因子：
5.2
作者：
Iacovino, Michelina;Bosnakovski, Darko;Fey, Holger;Rux, Danielle;Bajwa, Gagan;Mahen, Elisabeth;Mitanoska, Ana;Xu, Zhaohui;Kyba, Michael
通讯作者：
Kyba, Michael
DOI：
10.1242/dev.005868
发表时间：
2007-10
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Del Barrio MG;Taveira-Marques R;Muroyama Y;Yuk DI;Li S;Wines-Samuelson M;Shen J;Smith HK;Xiang M;Rowitch D;Richardson WD
通讯作者：
Richardson WD