Zinc-finger gene Fez in the olfactory sensory neurons regulates development of the olfactory bulb non-cell-autonomously

Zinc-finger gene Fez in the olfactory sensory neurons regulates development of the olfactory bulb non-cell-autonomously
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DOI:
10.1242/dev.02329
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发表时间:
2006-04-15
期刊:
影响因子:
4.6
通讯作者:
Hibi, M
Hibi, M
中科院分区:
生物学2区
文献类型:
--
作者:
Hirata, T;Nakazawa, M;Hibi, M

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Fez是一种锌指基因,编码一种转录抑制因子,在妊娠中期的嗅上皮、下丘脑、腹外侧腭和前丘脑中表达。为了揭示其功能,我们产生了Fez缺陷小鼠。Fez缺陷小鼠在嗅觉系统中显示出几种异常:(1)嗅觉感觉神经元的轴突投射受损;(2)嗅球尺寸减小;(3)嗅球中的异常层形成;以及(4)中间神经元祖细胞的异常吻侧迁移。Fez在投射神经元、中间神经元和中间神经元祖细胞中均不表达。转基因介导的Fez在嗅觉感觉神经元中的表达显著地挽救了Fez敲除小鼠中嗅觉轴突投射和嗅球形态发生的异常。因此,Fez是细胞自主需要的轴突终止的嗅觉感觉神经元,和Fez非细胞自主控制层的形成和interneuron的发展在嗅球。这些发现表明,来自嗅觉感觉神经元的信号有助于嗅球的正确形成。
Fez is a zinc-finger gene encoding a transcriptional repressor that is expressed in the olfactory epithelium, hypothalamus, ventrolateral pallium and prethalamus at mid-gestation. To reveal its function, we generated Fez-deficient mice. The Fez-deficient mice showed several abnormalities in the olfactory system: ( 1) impaired axonal projection of the olfactory sensory neurons; ( 2) reduced size of the olfactory bulb; ( 3) abnormal layer formation in the olfactory bulb; and ( 4) aberrant rostral migration of the interneuron progenitors. Fez was not expressed in the projection neurons, interneurons or interneuron progenitors. Transgene-mediated expression of Fez in olfactory sensory neurons significantly rescued the abnormalities in olfactory axon projection and in the morphogenesis of the olfactory bulb in Fez-knockout mice. Thus, Fez is cell-autonomously required for the axon termination of olfactory sensory neurons, and Fez non-cell-autonomously controls layer formation and interneuron development in the olfactory bulb. These findings suggest that signals from olfactory sensory neurons contribute to the proper formation of the olfactory bulb.