Developmental regulation of muscleblind-like (MBNL) gene expression in the chicken embryo retina

Developmental regulation of muscleblind-like (MBNL) gene expression in the chicken embryo retina
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DOI:
10.1002/dvdy.21408
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发表时间:
2008-01-01
影响因子:
2.5
通讯作者:
Adler, Ruben
Adler, Ruben
中科院分区:
生物学3区
文献类型:
--
作者:
Huang, Hu;Wahlin, Karl J.;Adler, Ruben

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肌盲样(MBNL)是一种含有CCCH锌指的RNA结合蛋白,是果蝇肌肉和光感受器发育所必需的;它在进化上是保守的,并且在人类中与肌肉疾病强直性肌营养不良症有关。然而,它在脊椎动物视网膜细胞发育中的作用仍然未知。作为其调查的初步方法,我们克隆了三个鸡muscleblind基因,其特征在于它们的异构体,并研究了它们在鸡胚视网膜中的表达模式。MBNL基因的相对表达水平在胚胎发育过程中增加。原位杂交(ISH)结果显示,该基因的表达与细胞凋亡密切相关。三种MBNL mRNA在所检测的所有发育阶段具有广泛的表达模式。有趣的是,用针对MBNL 1和MBNL 2的抗体通过免疫细胞化学检测到的蛋白质表达的时间和空间模式比ISH观察到的要严格得多。例如,在早期阶段(ED 5 -7),MBNL 1和MBNL 2 mRNA存在于整个视网膜中,但相应蛋白的免疫反应性主要限于视杯的周边(假定虹膜/睫状上皮/睫状边缘区)。MBNL 1和MBNL 2免疫反应性在后期在眼底变得可检测,但仅限于具有同源mRNA的ISH信号的细胞的非常小的子集(特别是神经节细胞和光感受器)。在光感受器内,MBNL 1和MBNL 2免疫反应性首先出现在它们的内段; MBNL 2仍然存在,但MBNL 1随后定位于它们的突触末端。这些表达模式是一致的可能性,MBNLs可能会调节感光细胞在小鸡视网膜的发展,MBL在果蝇,并建议MBNL 1和MBNL 2的表达可能会受到调节转录后。发展动力学237:286-296,2008年。(c)2007 Wiley-Liss,Inc.
Muscleblind-like (MBNL) is a CCCH zinc finger-containing RNA-binding protein required for the development of both muscle and photoreceptors in Drosophila; it is conserved evolutionarily, and it is associated in humans with the muscular disease myotonic dystrophy. Its role in the development of vertebrate retinal cells, however, remains unknown. As an initial approach to its investigation, we have cloned three chick muscleblind genes, characterized their isoforms, and examined their expression patterns in the chick embryo retina. The relative levels of expression of the MBNL genes increased during embryonic development. In situ hybridization (ISH) showed that the! three MBNL mRNAs had widespread patterns of expression at all the developmental stages examined. Of interest, the temporal and spatial patterns of protein expression, detected by immunocytochemistry with antibodies against MBNL1 and MBNL2, were much more restricted than those seen by ISH. At early stages (ED5-7), for example, MBNL1 and MBNL2 mRNAs were present throughout the retina, but immunoreactivity for the corresponding proteins was largely restricted to the periphery of the optic cup (presumptive iris/ciliary epithelium/ciliary margin zone). MBNL1 and MBNL2 immunoreactivity became detectable at the fundus at later stages, but was limited to a very small subset of the cells that had ISH signals for the cognate mRNAs (particularly ganglion cells and photoreceptors). Within photoreceptors, MBNL1 and MBNL2 immunoreactivity first appeared in their inner segments; MBNL2 remained there, but MBNL1 became subsequently localized to their synaptic terminals. These expression patterns are consistent with the possibility that MBNLs may regulate photoreceptor development in the chick retina, much as MBL does in Drosophila, and suggest that the expression of MBNL1 and MBNL2 may be regulated posttranscriptionally. Developmental Dynamics 237:286-296, 2008. (c) 2007 Wiley-Liss, Inc.