Patterning the zebrafish diencephalon by the conserved zinc-finger protein Fezl
Patterning the zebrafish diencephalon by the conserved zinc-finger protein Fezl
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DOI：
10.1242/dev.02705
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发表时间：
2007-01-01
期刊：
影响因子：
4.6
通讯作者：
Guo, Su
中科院分区：
文献类型：
--
作者：
Jeong, Jae-Yeon;Einhorn, Zev;Guo, Su
前脑构成中枢神经系统的最前部，并且在所有脊椎动物中在功能上至关重要且在结构上保守。它包括位于背侧的端脑和眼睛、位于腹侧的下丘脑和位于尾侧的间脑[从喙侧到尾侧：前丘脑、丘脑内界带（ZLI）、丘脑和前顶盖]。虽然已知拮抗Wnt蛋白可以确定端脑和眼睛的身份，但目前还不清楚间脑内如何建立各种细分-一个复杂的整合中心和脊椎动物大脑的中继站。保守的前脑特异性含锌指蛋白Fezl在调节脊椎动物前脑神经元分化中起着至关重要的作用。在这里，我们报告一个新的和必不可少的作用，斑马鱼Fezl在间脑内建立区域分区。首先，fezl的活性降低导致前丘脑的缺陷和ZLI的相应扩展。其次，Gal 4-UAS介导的fezl在晚期原肠胚中的过表达能够以ZLI和其他前脑和/或中脑区域为代价扩展前丘脑端脑和下丘脑。这种改变的大脑区域化之前，在未来间脑的wnt表达的早期下调。最后，fezl过表达能够恢复前前脑并下调无头和/或Tcf 3（也称为Tcf 7 l1 a）缺陷胚胎中的wnt表达。我们的研究结果表明，Fezl是至关重要的间脑内建立区域分区，也可能发挥作用的端脑和下丘脑的发展。
The forebrain constitutes the most anterior part of the central nervous system, and is functionally crucial and structurally conserved in all vertebrates. It includes the dorsally positioned telencephalon and eyes, the ventrally positioned hypothalamus, and the more caudally located diencephalon [ from rostral to caudal: the prethalamus, the zona limitans intrathalamica ( ZLI), the thalamus and the pretectum]. Although antagonizing Wnt proteins are known to establish the identity of the telencephalon and eyes, it is unclear how various subdivisions are established within the diencephalon - a complex integration center and relay station of the vertebrate brain. The conserved forebrain-specific zinc-finger-containing protein Fezl plays a crucial role in regulating neuronal differentiation in the vertebrate forebrain. Here, we report a new and essential role of zebrafish Fezl in establishing regional subdivisions within the diencephalon. First, reduced activity of fezl results in a deficit of the prethalamus and a corresponding expansion of the ZLI. Second, Gal4-UAS-mediated fezl overexpression in late gastrula is capable of expanding the prethalamus telencephalon and hypothalamus at the expense of the ZLI and other fore-and/or mid-brain regions. Such altered brain regionalization is preceded by the early downregulation of wnt expression in the prospective diencephalon. Finally, fezl overexpression is able to restore the anterior forebrain and downregulate wnt expression in Headless- and/or Tcf3 ( also known as Tcf7l1a)-deficient embryos. Our findings reveal that Fezl is crucial for establishing regional subdivisions within the diencephalon and may also play a role in the development of the telencephalon and hypothalamus.