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Spa 转录因子调控细胞增殖、存活和上皮完整性,其位于 Decapentaplegic 信号通路的下游。

The Spalt transcription factors regulate cell proliferation, survival and epithelial integrity downstream of the Decapentaplegic signalling pathway.

机构信息

Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Cantoblanco , Madrid 28049 , Spain.

出版信息

Biol Open. 2013 Jan 15;2(1):37-48. doi: 10.1242/bio.20123038. Epub 2012 Oct 26.

Abstract

The expression of the spalt genes is regulated by the Decapentaplegic signalling pathway in the Drosophila wing. These genes participate in the patterning of the longitudinal wing veins by regulating the expression of vein-specific genes, and in the establishment of cellular affinities in the central region of the wing blade epithelium. The Spalt proteins act as transcription factors, most likely regulating gene expression by repression, but the identity of their target genes in the wing is still unknown. As a preliminary step to unravel the genetic hierarchy controlled by the Spalt proteins, we have analysed their requirements during wing development, and addressed to what extent they mediate all the functions of the Decapentaplegic pathway in this developmental system. We identify additional functions for Spalt in cell division, survival, and maintenance of epithelial integrity. Thus, Spalt activity is required to promote cell proliferation, acting in the G2/M transition of the cell cycle. The contribution of Spalt to cell division is limited to the central region of the wing blade, as they do not mediate the extra growth triggered by Decapentaplegic signalling in the peripheral regions of the wing disc. In addition, Spalt function is required to maintain cell viability in cells exposed to high levels of Decapentaplegic signalling. This aspect of Spalt function is related to the repression of JNK signalling in the spalt domain of expression. Finally, we further characterise the requirements of Spalt to maintain epithelial integrity by regulating cellular affinities between cells located in the central wing region. Our results indicate that Spalt function mediates most of the requirements identified for Decapentaplegic signalling, contributing to establish the cellular qualities that differentiate central versus peripheral territories in the wing blade.

摘要

果蝇翅膀中 spalt 基因的表达受 Decapentaplegic 信号通路的调控。这些基因通过调节脉特异性基因的表达参与纵向翅脉的模式形成,并在翅膀刀片上皮细胞的中央区域建立细胞亲和力。Spalt 蛋白作为转录因子,最有可能通过抑制来调节基因表达,但它们在翅膀中的靶基因的身份仍不清楚。作为阐明 Spalt 蛋白调控的遗传层次结构的初步步骤,我们分析了它们在翅膀发育过程中的需求,并确定了它们在这个发育系统中在多大程度上介导了 Decapentaplegic 途径的所有功能。我们发现 Spalt 在细胞分裂、存活和维持上皮完整性方面具有额外的功能。因此,Spalt 活性需要促进细胞增殖,在细胞周期的 G2/M 转换中发挥作用。Spalt 对细胞分裂的贡献仅限于翅膀刀片的中央区域,因为它们不在翅膀盘的外围区域介导由 Decapentaplegic 信号触发的额外生长。此外,Spalt 功能需要维持暴露于高水平 Decapentaplegic 信号的细胞的细胞活力。Spalt 功能的这一方面与在表达 spalt 结构域中抑制 JNK 信号有关。最后,我们通过调节位于翅膀中央区域的细胞之间的细胞亲和力,进一步表征了 Spalt 维持上皮完整性的需求。我们的结果表明,Spalt 功能介导了为 Decapentaplegic 信号确定的大多数需求,有助于建立区分翅膀中央和外围区域的细胞特性。

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