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首页> 外文期刊>Development >vhnf1 integrates global RA patterning and local FGF signals to direct posterior hindbrain development in zebrafish.
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vhnf1 integrates global RA patterning and local FGF signals to direct posterior hindbrain development in zebrafish.

机译:vhnf1整合了全局RA模式和局部FGF信号,以指导斑马鱼的后脑发育。

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摘要

The vertebrate hindbrain is transiently divided along the anterior-posterior axis into seven morphologically and molecularly distinct segments, or rhombomeres, that correspond to Hox expression domains. The establishment of a proper 'hox code' is required for the development of unique rhombomere identities, including specification of neuronal fates. valentino (val), the zebrafish ortholog of mafB/Kreisler (Kr), encodes a bZip transcription factor that is required cell autonomously for the development of rhombomere (r) 5 and r6 and for activation of Hox group 3 gene expression. Recent work has demonstrated that the expression of val itself depends on three factors: retinoic acid (RA) signals from the paraxial mesoderm; fibroblast growth factor (Fgf) signals from r4; and variant hepatocyte nuclear factor 1 (vhnf1, also known as tcf2), a homeodomain transcription factor expressed posterior to the r4-5 boundary. We have investigated the interactions between these inputs onto val expression in the developing zebrafish hindbrain. We show that RA induces val expression via activation of vhnf1 expression in the hindbrain. Fgf signals from r4, acting through the MapK pathway, then cooperate with Vhnf1 to activate val expression and subsequent r5 and r6 development. Additionally, vhnf1 and val function as part of a multistep process required for the repression of r4 identity in the posterior hindbrain. vhnf1 acts largely independently of val to repress the r4 'hox code' posterior to the r4-5 boundary and therefore to block acquisition of r4-specific neuronal fates in the posterior hindbrain. However, vhnf1 is not able to repress all aspects of r4 identity equivalently. val is required downstream of vhnf1 to repress r4-like cell-surface properties, as determined by an 'Eph-ephrin code', by repressing ephrin-B2a expression in r5 and r6. The different requirements for vhnf1 and val to repress hoxb1a and ephrin-B2a, respectively, demonstrate that not all aspects of an individual rhombomere's identity are regulated coordinately.
机译:脊椎动物后脑沿前后轴被暂时分为七个形态和分子上不同的部分或菱形,分别对应于Hox表达域。建立独特的菱形身分,包括规范神经元命运,需要建立适当的“ hox码”。 mafB / Kreisler(Kr)的斑马鱼直系同源物valentino(val)编码bZip转录因子,它是rhombomere(r)5和r6的发育以及激活Hox 3组基因表达所必需的细胞。最近的研究表明,val本身的表达取决于三个因素:来自近轴中胚层的视黄酸(RA)信号;来自r4的成纤维细胞生长因子(Fgf)信号;变体肝细胞核因子1(vhnf1,也称为tcf2),即在r4-5边界后表达的同源域转录因子。我们已经研究了这些输入之间的相互作用对发育中的斑马鱼后脑中val表达的影响。我们显示RA通过激活后脑中的vhnf1表达来诱导val表达。来自r4的Fgf信号通过MapK途径起作用,然后与Vhnf1协同激活val表达以及随后的r5和r6发育。此外,vhnf1和val是抑制后后脑r4同一性所需的多步过程的一部分。 vhnf1的作用与val无关,它可以抑制r4-5边界后的r4'hox码',从而阻止后脑后部r4特异性神经元命运的获得。但是,vhnf1不能等效地抑制r4身份的所有方面。 vhnf1的下游需要val来通过抑制r5和r6中的ephrin-B2a表达来抑制r4样细胞表面特性(由“弗弗蛋白”决定)。对vhnf1和val分别抑制hoxb1a和ephrin-B2a的不同要求表明,并非单个菱形的身份的所有方面都受到协调调节。

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