Molecular signals regulating proliferation of stem and progenitor cells in mouse olfactory epithelium
Molecular signals regulating proliferation of stem and progenitor cells in mouse olfactory epithelium
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DOI：
10.1159/000082135
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发表时间：
2004-01-01
影响因子：
2.9
通讯作者：
Calof, AL
中科院分区：
文献类型：
--
作者：
Kawauchi, S;Beites, CL;Calof, AL
为了了解信号分子如何调节神经元从增殖干细胞和神经元祖细胞在发育和再生的神经系统中的产生，我们研究了模型神经源性上皮，小鼠的嗅上皮（OE）中的神经发生。我们的研究采用了一种候选方法来测试在调节神经发生中具有潜在重要性的信号分子，并利用了包括组织培养、原位杂交和小鼠遗传学在内的方法。使用这些方法，我们已经确定了三个不同的阶段的干细胞和过境放大祖细胞的分化途径的嗅觉受体神经元（ORN），并确定了机制，这些祖细胞类型的每一个的发展是由内产生的信号OE本身和其底层基质。我们的研究结果表明，嗅觉神经发生的调节是严重依赖于多个信号分子从两个不同的多肽生长因子超家族，成纤维细胞生长因子和转化生长因子β（TGF-β）组。此外，他们指出，这些信号分子至少以两种重要方式相互作用：首先，相反的信号在ORN通路中会聚在特定发育阶段的细胞上，以调节增殖和分化;其次，这些信号分子--特别是TGF-β及其拮抗剂--在调节祖细胞池大小从而调节神经元数量的反馈回路中发挥关键作用，在发育和再生过程中。版权所有（C）2004 S. Karger AG，巴塞尔。
To understand how signaling molecules regulate the generation of neurons from proliferating stem cells and neuronal progenitors in the developing and regenerating nervous system, we have studied neurogenesis in a model neurogenic epithelium, the olfactory epithelium (OE) of the mouse. Our studies have employed a candidate approach to test signaling molecules of potential importance in regulating neurogenesis and have utilized methods that include tissue culture, in situ hybridization and mouse genetics. Using these approaches, we have identified three distinct stages of stem and transit amplifying progenitor cells in the differentiation pathway of olfactory receptor neurons (ORNs) and have identified mechanisms by which the development of each of these progenitor cell types is regulated by signals produced both within the OE itself and by its underlying stroma. Our results indicate that regulation of olfactory neurogenesis is critically dependent on multiple signaling molecules from two different polypeptide growth factor superfamilies, the fibroblast growth factors and the transforming growth factor beta (TGF-beta) group. In addition, they indicate that these signaling molecules interact in at least two important ways: first, opposing signals converge on cells at specific developmental stages in the ORN pathway to regulate proliferation and differentiation; and second, these signaling molecules - particularly the TGF-betas and their antagonists - play key roles in feedback loops that regulate the size of progenitor cell pools and thereby neuron number, during development and regeneration. Copyright (C) 2004 S. Karger AG, Basel.