Regulation of tissue morphogenesis by non-canonical steroid hormone signaling in Drosophila

果蝇中非典型类固醇激素信号传导对组织形态发生的调节

• 批准号: RGPIN-2018-04300
• 负责人: Harden, Nicholas
• 金额: $ 7.29万
• 依托单位: Simon Fraser University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=761195
• 关键词: Regulation; tissue; morphogenesis; non; canonical

During the development of embryos, there is a need to close holes in sheets of cells called epithelia. Failure of such closure events can lead to birth defects such as spina bifida and cleft lip and palate. Developmental epithelial closure is very similar to the healing of a wound, and the two processes use the same cellular machinery. Indeed, developmental epithelial closures can be considered as wound healing events. We are studying genes involved in a developmental wound healing event called dorsal closure that occurs during embryonic development in the fruit fly Drosophila. We use this organism due to the advanced genetic tools available and the ease with which dorsal closure can be observed. This work is relevant to human wound healing, as much of the cellular machinery has already been characterized, and is the same in humans and fruit flies. We are asking an important question with regard to Drosophila dorsal closure: how does communication between cells lead to smooth closure of the wound? In particular, we are working to understand how a steroid hormone called ecdysone can regulate the timing of genes that are being turned on to close the hole. Preliminary results indicate that ecdysone acts through an atypical pathway to turn on these genes, but interestingly, the same pathway is sometimes used by human steroid hormones such as estrogen. This result suggests that steroid hormones have been using this atypical pathway for hundreds of millions of years, before fruit flies diverged from humans. There are a number of potential benefits from this research. First, we can learn about the evolution of steroid hormone signaling, a cell communication process important in development and disease. Second, it will increase our understanding of the cellular events behind the closure of epithelial sheets both during development and in the healing of wounds. Third, this work will give important insight into the regulation of the movement and shape of epithelial cells, which is a key process in building a multicellular organism.

在胚胎发育过程中，需要关闭称为上皮细胞的细胞片中的孔。这种闭合事件的失败可能导致出生缺陷，例如脊柱裂和唇腭裂。发育中的上皮闭合与伤口愈合非常相似，这两个过程使用相同的细胞机制。事实上，发育上皮闭合可以被认为是伤口愈合事件。我们正在研究与果蝇胚胎发育过程中发生的称为背侧闭合的发育伤口愈合事件有关的基因。我们使用这种生物体是由于先进的遗传工具和容易与背部关闭可以观察到。这项工作与人类伤口愈合有关，因为大部分细胞机制已经被表征，并且在人类和果蝇中是相同的。 我们正在问一个关于果蝇背部闭合的重要问题：细胞之间的交流如何导致伤口的顺利闭合？特别是，我们正在努力了解一种叫做蜕皮激素的类固醇激素是如何调节基因关闭漏洞的时间的。初步结果表明，蜕皮激素通过一种非典型途径来激活这些基因，但有趣的是，人类类固醇激素（如雌激素）有时也使用相同的途径。这一结果表明，类固醇激素已经使用这种非典型途径数亿年，在果蝇从人类分化出来之前。这项研究有许多潜在的好处。首先，我们可以了解类固醇激素信号的演变，这是一个在发育和疾病中很重要的细胞通讯过程。第二，它将增加我们对发育和伤口愈合过程中上皮层闭合背后的细胞事件的理解。第三，这项工作将对上皮细胞的运动和形状的调节提供重要的见解，这是构建多细胞生物体的关键过程。