Six1 and Six4 promote survival of sensory neurons during early trigeminal gangliogenesis
Six1 and Six4 promote survival of sensory neurons during early trigeminal gangliogenesis
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DOI：
10.1016/j.brainres.2006.07.103
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发表时间：
2006-10-20
期刊：
影响因子：
2.9
通讯作者：
Kawakami, Kiyoshi
中科院分区：
文献类型：
--
作者：
Konishi, Yoshiyuki;Ikeda, Keiko;Kawakami, Kiyoshi
感觉神经元的存活受到细胞类型和发育阶段特异性方式的严格调节。这种调节的转录调控机制仍有待阐明。在本研究中，我们研究了Six 1和Six 4在三叉神经节发育中的作用。Six 1和Six 4在三叉神经节形成早期的感觉神经元中表达丰富。Six 1和Six 4在小鼠中的损失引起三叉神经节中的严重缺陷，其中在神经节形成的早期而非晚期观察到伴随着半胱天冬酶-3活化的大量细胞凋亡。在Six 1（-/-）Six 4（-/-）小鼠中，产生了三叉神经感觉神经元，但与野生型小鼠相比，Bcl-x的表达减少。因此，即使存在神经营养素，缺陷小鼠的神经元也无法在培养物中存活。我们的研究结果表明，Six 1和Six 4在早期生成的三叉神经感觉神经元的生存细胞内在的作用。(c)2006 Elsevier B. V.保留所有权利。
Survival of sensory neurons is tightly regulated in cell-type and developmental-stage specific manners. The transcriptional regulatory mechanisms underlying this regulation remain to be elucidated. In the present study, we investigated the role of Six1 and Six4 in the development of trigeminal ganglia. Abundant expression of Six1 and Six4 was noted in sensory neurons during early trigeminal gangliogenesis. Loss of both Six1 and Six4 in mice caused severe defects in the trigeminal ganglia, wherein massive apoptosis accompanied by activation of caspase-3 was observed at early but not late stages of gangliogenesis. In Six1(-/-)Six4(-/-) mice, trigeminal sensory neurons were generated, but showed reduced expression of Bcl-x compared with the wild-type mice. Accordingly, neurons from the deficient mice could not survive in culture even in the presence of neurotrophins. Our results suggest a cell-intrinsic role of Six1 and Six4 in the survival of early-generated trigeminal sensory neurons. (c) 2006 Elsevier B.V. All rights reserved.