Different combinations of Notch ligands and receptors regulate V2 interneuron progenitor proliferation and V2a/V2b cell fate determination
Different combinations of Notch ligands and receptors regulate V2 interneuron progenitor proliferation and V2a/V2b cell fate determination
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Notch配体和受体的不同组合调节V2中间神经元祖细胞增殖和V2a/V2b细胞命运决定
DOI：
10.1016/j.ydbio.2014.04.011
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发表时间：
2014
影响因子：
2.7
通讯作者：
M.
中科院分区：
文献类型：
--
作者：
Okigawa;S.;Mizoguchi;T.;Okano;M.;Tanaka;H.;Isoda;M.;Jiang;Y.J.;Suster;M.;Higashijima;S.-I.;Kawakami;K.;and Itoh;M.
神经元的广泛多样性对神经元功能至关重要。在脊椎动物发育过程中，脊髓是由中间神经元和正在进行的神经发生协调的感觉和运动任务的场所。在脊髓中，V2-中间神经元（V2-IN）祖细胞（p2）发育成兴奋性V2 a-IN和抑制性V2 b-IN。这两种类型的中间神经元的平衡需要精确控制其产生的数量和时间。在这里，使用斑马鱼胚胎与改变Notch信号，我们表明，不同的Notch配体和受体的组合调节两个功能：维持p2祖细胞和V2 a/V2 b细胞的命运决定V2-IN发展。两个配体，DeltaA和DeltaD，和三个受体，Notch 1a，Notch 1b和Notch 3冗余地有助于p2祖细胞的维持。另一方面，DeltaA、DeltaC和Notch 1a主要参与V2 a/V2 b细胞命运的决定。激活Notch配体的泛素连接酶Mib通过其激活DeltaA、DeltaC和DeltaD而在两种功能中起作用。此外，p2祖细胞的维护和V2 a/V2 b命运的决定是不是不同的时间过程，但在同一时间框架内发生在发展。总之，V2-IN细胞祖细胞增殖和V2 a/V2 b细胞命运决定涉及通过在斑马鱼发育过程中同时发生的不同组Notch配体-受体组合的信号传导。
The broad diversity of neurons is vital to neuronal functions. During vertebrate development, the spinal cord is a site of sensory and motor tasks coordinated by interneurons and the ongoing neurogenesis. In the spinal cord, V2-interneuron (V2-IN) progenitors (p2) develop into excitatory V2a-INs and inhibitory V2b-INs. The balance of these two types of interneurons requires precise control in the number and timing of their production. Here, using zebrafish embryos with altered Notch signaling, we show that different combinations of Notch ligands and receptors regulate two functions: the maintenance of p2 progenitor cells and the V2a/V2b cell fate decision in V2-IN development. Two ligands, DeltaA and DeltaD, and three receptors, Notch1a, Notch1b, and Notch3 redundantly contribute to p2 progenitor maintenance. On the other hand, DeltaA, DeltaC, and Notch1a mainly contribute to the V2a/V2b cell fate determination. A ubiquitin ligase Mib, which activates Notch ligands, acts in both functions through its activation of DeltaA, DeltaC, and DeltaD. Moreover, p2 progenitor maintenance and V2a/V2b fate determination are not distinct temporal processes, but occur within the same time frame during development. In conclusion, V2-IN cell progenitor proliferation and V2a/V2b cell fate determination involve signaling through different sets of Notch ligand–receptor combinations that occur concurrently during development in zebrafish.