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新型丝氨酸/苏氨酸激酶基因Ulk4在非洲爪蟾前脑发育过程中神经祖细胞中的表达。

Expression of a novel serine/threonine kinase gene, Ulk4, in neural progenitors during Xenopus laevis forebrain development.

作者信息

Domínguez L, Schlosser G, Shen S

机构信息

Regenerative Medicine Institute (REMEDI), School of Medicine and School of Natural Sciences, National University of Ireland (NUI) Galway, Galway, Ireland.

Regenerative Medicine Institute (REMEDI), School of Medicine and School of Natural Sciences, National University of Ireland (NUI) Galway, Galway, Ireland.

出版信息

Neuroscience. 2015 Apr 2;290:61-79. doi: 10.1016/j.neuroscience.2014.12.060. Epub 2015 Jan 28.

Abstract

We have analyzed the expression pattern of a novel serine/threonine kinase gene Ulk4 during forebrain development in Xenopus laevis. To this aim, we firstly cloned a Ulk4 cDNA fragment from X.laevis and generated a RNA probe that was used for its detection by in situ hybridization. Throughout development xUlk4 expression was detected along the ventricular (vz) and subventricular zones (svz) of all forebrain regions, with the exception of the vz of the striatum. In the adult, xUlk4 was also mainly located in the vz, with some xUlk4 expressing cells reaching the svz/mantle zone (mz). This xUlk4 expression was especially remarkable in forebrain regions involving the homeostatic control of the brain such as the preoptic region, the hypothalamic territory and some neurosecretory circumventricular organs (CVOs). We further combined in situ hybridization for xUlk4 with immunohistochemistry for the neural progenitor cell marker SOX3, the radial glial marker brain lipid-binding protein (BLBP), neuronal markers MAP2 and doublecortin (DCX) and the specific neuronal marker tyrosine hydroxylase (TH). xUlk4 was co-expressed with the neural stem/progenitor cell marker SOX3 in the vz of all the forebrain regions throughout development and in the adult, and this co-expression was also especially evident in the svz of the hypothalamic region. xUlk4 was also expressed in the radial glia along the whole brain. We have also found minor expression of xUlk4 in some DCX- or MAP2-positive cells but not in TH-positive neurons. These findings suggest that Ulk4 may play roles in neural stem/progenitor cells during neurogenesis both in development and in the adulthood, in migrating cells as well as in cells committed to neuronal fate in Xenopus. Moreover, the results obtained in this study argue for an involvement of Ulk4 in the control of the neuroendocrine homeostatic functions in the brain.

摘要

我们分析了非洲爪蟾前脑发育过程中一个新的丝氨酸/苏氨酸激酶基因Ulk4的表达模式。为此,我们首先从非洲爪蟾中克隆了一个Ulk4 cDNA片段,并制备了一个RNA探针,用于原位杂交检测。在整个发育过程中,除纹状体的脑室区(vz)外,在所有前脑区域的脑室区(vz)和室下区(svz)均检测到xUlk4的表达。在成体中,xUlk4也主要位于脑室区,一些表达xUlk4的细胞延伸至室下区/套层区(mz)。这种xUlk4的表达在前脑区域尤其显著,这些区域参与大脑的稳态控制,如视前区、下丘脑区域和一些神经分泌性室周器官(CVOs)。我们进一步将xUlk4的原位杂交与神经祖细胞标志物SOX3、放射状胶质细胞标志物脑脂质结合蛋白(BLBP)、神经元标志物MAP2和双皮质素(DCX)以及特定神经元标志物酪氨酸羟化酶(TH)的免疫组织化学相结合。在整个发育过程和成体中,xUlk4与神经干/祖细胞标志物SOX3在前脑所有区域的脑室区共表达,并且这种共表达在下丘脑区域的室下区也尤为明显。xUlk4也在整个大脑的放射状胶质细胞中表达。我们还发现xUlk4在一些DCX或MAP2阳性细胞中有少量表达,但在TH阳性神经元中不表达。这些发现表明,Ulk4在非洲爪蟾发育和成体神经发生过程中,可能在神经干/祖细胞、迁移细胞以及已确定为神经元命运的细胞中发挥作用。此外,本研究获得的结果表明Ulk4参与大脑神经内分泌稳态功能的控制。

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