FGF signaling is required for determination of otic neuroblasts in the chick embryo
FGF signaling is required for determination of otic neuroblasts in the chick embryo
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DOI：
10.1016/j.ydbio.2003.11.012
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发表时间：
2004-03-01
影响因子：
2.7
通讯作者：
Giraldez, F
中科院分区：
文献类型：
--
作者：
Alsina, B;Abelló, G;Giraldez, F
内在和外在因素之间的相互作用是必不可少的过渡到不同的细胞状态在发展过程中。我们分析了在耳神经元发育的早期阶段FGF10和FGF信号的表达和功能。FGF10在鸡耳基板的假定神经源性区域重叠的高度限制性结构域中表达。对FGF10、前神经和神经源性基因表达模式的详细研究揭示了以下基因表达开始的时间顺序：FGF10> Ngn 1/Delta1/Nes 5> NeuroD/NeuroM。FGF 10和FGF受体抑制对细胞决定和细胞增殖产生相反的作用。体内FGF 10的异位表达促进NeuroD和NeuroM表达的增加。BrdU掺入实验表明，NeuroD表达细胞的增加不是由于细胞增殖的增加。在耳外植体中抑制FGF受体信号传导导致神经生成素1、NeuroD、Delta1和Hes5表达严重减少，而非神经基因如Lmx1没有变化。然而，它不干扰CVG内的NeuroD表达或神经母细胞分层。FGF抑制引起的前神经基因表达的丧失不是由细胞增殖减少或细胞死亡增加引起的。我们认为，在耳上皮细胞中的FGF信号传导是神经元前体细胞从细胞分裂中退出和不可逆地承诺神经元的命运所必需的。(C)2003年爱思唯尔公司All rights reserved.
The interplay between intrinsic and extrinsic factors is essential for the transit into different cell states during development. We have analyzed the expression and function of FGF10 and FGF-signaling during the early stages of the development of otic neurons. FGF10 is expressed in a highly restricted domain overlapping the presumptive neurogenic region of the chick otic placode. A detailed study of the expression pattern of FGF10, proneural, and neurogenic genes revealed the following temporal sequence for the onset of gene expression: FGF10>Ngn1/Delta1/Nes5>NeuroD/NeuroM. FGF10 and FGF receptor inhibition cause opposed effects on cell determination and cell proliferation. Ectopic expression of FGF 10 in vivo promotes an increase in NeuroD and NeuroM expression. BrdU incorporation experiments showed that the increase in NeuroD-expressing cells is not due to an increase in cell proliferation. Inhibition of FGF receptor signaling in otic explants causes a severe reduction in Neurogenin1, NeuroD, Delta1, and Hes5 expression with no change in non-neural genes like Lmx1. However, it does not interfere with NeuroD expression within the CVG or with neuroblast delamination. The loss of proneural gene expression caused by FGF inhibition is not caused by decreased cell proliferation or by increased cell death. We suggest that FGF signaling in the otic epithelium is required for neuronal precursors to withdraw from cell division and irreversibly commit to neuronal fate. (C) 2003 Elsevier Inc. All rights reserved.