Regulatory principles of echinoderm metamorphosis

有些动物直接从胚胎发育成成虫，而有些动物则处于中间幼虫阶段。幼虫到成虫形式的蜕变或多或少是戏剧性的，在棘皮动物的情况下，涉及身体对称的巨大变化，从两侧的幼虫到五边形的成虫（五向对称）。成虫首先以一组细胞的形式生长，这是在幼虫体内生长的“雏形”，最后从幼虫中生长出来。虽然这一过程依赖于与胚胎发育相同的发育基因，但这些基因是由基因组编码的另一种发育程序调动的。我想了解这两个控制从卵到幼虫和从幼虫到五元体成虫发育的调控程序是如何在同一个基因组中共存的。基因是由调控元件控制的，这些DNA片段被称为转录因子的特殊蛋白质结合在一起。我想确定基因组中控制幼虫蜕变为具有另一种身体对称的成虫的调控元件是什么，以及哪些转录因子在调动这些元件方面发挥了最重要的作用。我们将使用基于测序的技术，如单细胞转录组学和计算分析来找出这个问题。然后，我们将在这些启动子的控制下，使用携带荧光蛋白编码基因的转基因海胆幼虫来监测这些调节元件的活性。棘皮动物的基因组具有很强的可塑性，这意味着基因顺序可以改变，一些人认为这可能在基因重组调控中发挥了关键作用。为了验证这一观点，我们将评估发生在不同棘皮动物谱系中的基因组变化。然后，由于调控元件嵌入被称为三维染色质室的DNA环中，我们将看到它们在变形过程中是否受到影响，并最终建立一个雏形发育的综合模型。我们希望发现新的调控途径，使这些迷人的生物进化出新的身体计划成为可能。

While some animals develop directly from embryos into their adult forms, others present an intermediate larval stage. The metamorphosis of the larva into the adult form can be more or less dramatic, and, in the case of echinoderms, involve a drastic change in body symmetry from a bilateral larva into a pentaradial adult (five-way symmetry). The adult first grows as a set of cells, the 'rudiment' that grows within the larva and finally everts from it. While this process relies on the same development genes as embryonic development, these genes are mobilised by an alternative developmental program encoded in the genome. I want to understand how these two regulatory programs that control development from egg to larva and from larva to pentaradial adult can coexist in the same genome. Genes are controlled by regulatory elements, segments of DNA that are bound by specialised proteins called transcription factors. I want to determine what are the regulatory elements in the genome that control the metamorphosis of the larval into an adult with an alternative body symmetry and which transcription factors play the most important role in mobilising these elements. We will use sequencing-based technologies, such as single-cell transcriptomics and computational analyses to find this out. We will then use transgenic sea urchin larvae carrying a gene encoding for a fluorescent protein under the control of such promoters to monitor where these regulatory elements are active. Echinoderm genomes are quite plastic, which means gene order can change and some have postulated that this could have played a key role in rewiring gene regulation. To test this idea, we will evaluate the genomic changes that took place in different echinoderm lineages. Then, as regulatory elements are embedded in loops of DNA known as three-dimensional chromatin compartments, we will see if these are affected during metamorphosis, and finally build an integrative model of rudiment development. We expect to uncover the new regulatory route that has made possible the evolution of a new body plan in these mesmerising organisms.