EXPRESSION OF THE ZINC-FINGER GENE PLZF AT RHOMBOMERE BOUNDARIES IN THE VERTEBRATE HINDBRAIN

EXPRESSION OF THE ZINC-FINGER GENE PLZF AT RHOMBOMERE BOUNDARIES IN THE VERTEBRATE HINDBRAIN
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DOI:
10.1073/pnas.92.6.2249
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发表时间:
1995-03-14
影响因子:
11.1
通讯作者:
ZELENT, A
ZELENT, A
中科院分区:
综合性期刊1区
文献类型:
--
作者:
COOK, M;GOULD, A;ZELENT, A

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为了研究PLZF基因的潜在生物学作用,我们分离了其鼠同源物(mPLZF)并研究了其发育表达模式。PLZF基因是在患有t(11;17)染色体易位的急性早幼粒细胞白血病患者中发现的与RARA基因座的融合基因。mPLZF mRNA的水平在围产期增加的肝脏,心脏和肾脏,但除了心脏,他们要么不存在或非常低的成年组织。在小鼠胚胎发育7.0和10.5天之间的mPLZF表达的原位分析显示,mPLZF mRNA和蛋白质在中枢神经系统中以空间限制和时间动态模式共表达。在后脑区域,节段性的表达模式与菱形的发展。从9.0天的发展,首先开始在菱形3和5,有一个有序的下调表达的中心,每个菱形,使1天后升高水平的mPLZF mRNA和蛋白质被限制在细胞周围的菱形边界。我们也克隆了PLZF基因的鸡同源物,在后脑中表现出类似的节段性表达模式。迄今为止,PLZF代表了在菱形边界具有升高表达的转录因子的唯一实例。哺乳动物和鸟类中枢神经系统发育过程中PLZF表达模式之间的高度进化保守性表明,它在脊椎动物后脑的区域化中具有重要的功能作用,可能调节边界细胞的相互作用。
To investigate the potential biological role(s) of the PLZF gene, discovered as a fusion with the RARA Locus in a patient with acute promyelocytic leukemia harboring a t(11;17) chromosomal translocation, we have isolated its murine homologue (mPLZF) and studied its patterns of developmental expression. The levels of mPLZF mRNAs increased perinatally in the liver, heart, and kidney, but with the exception of the heart, they were either absent or very low in the adult tissues. In situ analysis of mPLZF expression in mouse embryos between 7.0 and 10.5 days of development revealed that mPLZF mRNAs and proteins were coexpressed in spatially restricted and temporally dynamic patterns in the central nervous system. In the hindbrain region, a segmental pattern of expression correlated with the development of the rhombomeres. From 9.0 days of development, starting first in rhombomeres 3 and 5, there was an ordered down-regulation of expression in the center of each rhombomere, so that 1 day later elevated levels of mPLZF mRNAs and proteins were restricted to cells surrounding the rhombomeric boundaries. The chicken homologue of the PLZF gene, which we have also cloned, demonstrated a similar segmental pattern of expression in the hindbrain. To date, PLZF represents the only example of a transcription factor with elevated expression at rhombomeric boundaries. The high degree of evolutionary conservation between the patterns of PLZF expression during mammalian and avian central nervous system development suggests that it has an important functional role in the regionalization of the vertebrate hindbrain, potentially regulating boundary cell interactions.