摘要
背景:基本helix-loop-helix(bHLH)蛋白家族是一类转录因子,它们与细胞增殖有关,组织分化,以及其他重要的开发过程。我们报道,核本地化蛋白1(Nulp1)可能作为小说bHLH转录因子调节细胞功能。但是,它在发展中的作用体内仍然未知。 方法:Nulp1(dNulp1)突变体是由CRISPR / Cas9针对未知函数的域(DUF654)的C末端。Wg目标基因的表达分析中存在。我们使用Top-Flash荧光素酶记者分析应对Wg信号。 结果:在这里,我们表明,果蝇Nulp1(dNulp1)突变体,由CRISPR / Cas9针对未知函数的域(DUF654)的C末端,部分纯合子的致命的和罕见的幸免型股骨弯曲,类似于先天性bent-bone发育不良的主要表现在人类Stuve——Weidemann综合症。苍蝇表型可以获救dNulp1表达,表明dNulp1飞股骨发展和生存至关重要。此外,dNulp1过度抑制造成的切口翼表型过度sgg / GSK3β规范化Wnt级联的抑制剂。此外,存在积极分析显示,七个目标基因受Wg信号通路抑制在响应dNulp1击倒,而两个负监管工作组目标上调dNulp1突变体。最后,dNulp1超表达显著激活Top-Flash Wnt信号记者。 结论:bHLH蛋白质dNulp1股骨发展和生存至关重要的果蝇作为一个积极的辅助因子在Wnt /无翼的信号。
关键词: bHLH、dNulp1 CRISPR / Cas9 Wnt / Wg信号
Current Molecular Medicine
Title:The bHLH Protein Nulp1 is Essential for Femur Development Via Acting as a Cofactor in Wnt Signaling in Drosophila
Volume: 17 Issue: 7
关键词: bHLH、dNulp1 CRISPR / Cas9 Wnt / Wg信号
摘要: Background: The basic helix-loop-helix (bHLH) protein families are a large class of transcription factors, which are associated with cell proliferation, tissue differentiation, and other important development processes. We reported that the Nuclear localized protein-1 (Nulp1) might act as a novel bHLH transcriptional factor to mediate cellular functions. However, its role in development in vivo remains unknown.
Methods: Nulp1 (dNulp1) mutants are generated by CRISPR/Cas9 targeting the Domain of Unknown Function (DUF654) in its C terminal. Expression of Wg target genes are analyzed by qRT-PCR. We use the Top-Flash luciferase reporter assay to response to Wg signaling.
Results: Here we show that Drosophila Nulp1 (dNulp1) mutants, generated by CRISPR/Cas9 targeting the Domain of Unknown Function (DUF654) in its C terminal, are partially homozygous lethal and the rare escapers have bent femurs, which are similar to the major manifestation of congenital bent-bone dysplasia in human Stuve- Weidemann syndrome. The fly phenotype can be rescued by dNulp1 over-expression, indicating that dNulp1 is essential for fly femur development and survival. Moreover, dNulp1 overexpression suppresses the notch wing phenotype caused by the overexpression of sgg/GSK3β, an inhibitor of the canonical Wnt cascade. Furthermore, qRT-PCR analyses show that seven target genes positively regulated by Wg signaling pathway are down-regulated in response to dNulp1 knockout, while two negatively regulated Wg targets are up-regulated in dNulp1 mutants. Finally, dNulp1 overexpression significantly activates the Top-Flash Wnt signaling reporter.
Conclusion: We conclude that bHLH protein dNulp1 is essential for femur development and survival in Drosophila by acting as a positive cofactor in Wnt/Wingless signaling.
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Cite this article as:
The bHLH Protein Nulp1 is Essential for Femur Development Via Acting as a Cofactor in Wnt Signaling in Drosophila, Current Molecular Medicine 2017; 17 (7) . https://dx.doi.org/10.2174/1566524018666180212145714
DOI https://dx.doi.org/10.2174/1566524018666180212145714 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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