转录因子Zfp423/OAZ是小脑发育和中枢神经系统中线模式形成所必需的。
The transcription factor Zfp423/OAZ is required for cerebellar development and CNS midline patterning.
作者信息
Cheng Li E, Zhang Jiangyang, Reed Randall R
机构信息
Center for Sensory Biology, Department of Molecular Biology and Genetics, Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
出版信息
Dev Biol. 2007 Jul 1;307(1):43-52. doi: 10.1016/j.ydbio.2007.04.005. Epub 2007 Apr 12.
Abstract
The dorsal midline structure is critical for patterning the developing central nervous system (CNS). We show here that Zfp423/OAZ, a multiple zinc-finger transcription factor involved in both OE/EBF and BMP-signaling pathways, is required for the proper formation of forebrain and hindbrain midline structures. During embryogenesis, OAZ is highly expressed at the dorsal neuroepithelium flanking the roof plate. OAZ-deficient mice are ataxic, attributed to the reduction of the cerebellar vermis and some regions of the hemispheres. Characterization of postnatal cerebellar development shows defects in Purkinje cell differentiation and granule cell proliferation. In the forebrain, dorsal telencephalic commissural neurons project axons, but these axons fail to cross the midline and midline glial cells are abnormally distributed. Moreover, there are malformations in midline structures including the septum, thalamus and hypothalamus, suggesting a pivotal role of OAZ in CNS midline patterning.
摘要
背侧中线结构对于发育中的中枢神经系统（CNS）的模式形成至关重要。我们在此表明，Zfp423/OAZ是一种参与OE/EBF和BMP信号通路的多锌指转录因子，对于前脑和后脑中线结构的正常形成是必需的。在胚胎发生过程中，OAZ在顶板两侧的背侧神经上皮中高度表达。OAZ缺陷小鼠共济失调，这归因于小脑蚓部和半球某些区域的减少。对出生后小脑发育的特征分析显示浦肯野细胞分化和颗粒细胞增殖存在缺陷。在前脑中，背侧端脑连合神经元投射轴突，但这些轴突未能穿过中线，并且中线神经胶质细胞分布异常。此外，包括隔膜、丘脑和下丘脑在内的中线结构存在畸形，这表明OAZ在CNS中线模式形成中起关键作用
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