Linking Asymmetric Cell Division to the Terminal Differentiation Program of Postmitotic Neurons in C. elegans
Linking Asymmetric Cell Division to the Terminal Differentiation Program of Postmitotic Neurons in C. elegans
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DOI：
10.1016/j.devcel.2009.02.011
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发表时间：
2009-04-21
影响因子：
11.8
通讯作者：
Hobert, Oliver
中科院分区：
文献类型：
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作者：
Bertrand, Vincent;Hobert, Oliver
不对称分裂如何与神经元亚型的终末分化程序联系在一起还知之甚少。In C.在线虫中，两种同源域转录因子TTX-3（LHX 2/9直系同源物）和CEH-10（CHX 10直系同源物）直接激活胆碱能中间神经元AIY中的大量终末分化基因。我们在这里建立了一个转录级联连接不对称分裂这个分化程序。由Zic因子REF-2和bHLH因子HLH-2形成的瞬时谱系特异性输入直接激活AN母亲中的ttx-3表达。在AIY母体的终末分裂期间，不对称Wnt/β-连环蛋白途径与TTX-3合作，直接将ceh-10表达限制在两个子细胞中的仅一个。TTX-3和CEH-10自动维持其表达，从而锁定在分化状态。我们的研究确定了瞬时谱系和不对称分裂输入是如何整合的，并表明Wnt/β-连环蛋白通路被广泛用于控制神经元谱系的身份。
How asymmetric divisions are connected to the terminal differentiation program of neuronal subtypes is poorly understood. In C. elegans, two homeodomain transcription factors, TTX-3 (a LHX2/9 ortholog) and CEH-10 (a CHX10 ortholog), directly activate a large battery of terminal differentiation genes in the cholinergic interneuron AIY. We establish here a transcriptional cascade linking asymmetric division to this differentiation program. A transient lineage-specific input formed by the Zic factor REF-2 and the bHLH factor HLH-2 directly activates ttx-3 expression in the AN mother. During the terminal division of the AIY mother, an asymmetric Wnt/beta-catenin pathway cooperates with TTX-3 to directly restrict ceh-10 expression to only one of the two daughter cells. TTX-3 and CEH-10 automaintain their expression, thereby locking in the differentiation state. Our study establishes how transient lineage and asymmetric division inputs are integrated and suggests that the Wnt/beta-catenin pathway is widely used to control the identity of neuronal lineages.