Architecture and evolution of the cis-regulatory system of the echinoderm kirrelL gene.
Architecture and evolution of the cis-regulatory system of the echinoderm kirrelL gene.
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DOI：
10.7554/elife.72834
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发表时间：
2022-02-25
期刊：
影响因子：
7.7
通讯作者：
Ettensohn CA
中科院分区：
文献类型：
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作者：
Khor JM;Ettensohn CA
棘皮动物骨骼发生的基因调控网络（GRN）是GRN结构和进化的重要模型。KirrelL是该网络中的重要下游效应基因，编码骨骼发生细胞融合和骨骼形成所需的Ig超家族蛋白。在这项研究中，我们解剖了紫海胆，球海胆kirrelL基因的转录控制区。使用质粒和细菌人工染色体为基础的转基因报告基因检测，我们确定了关键的顺式调控元件（克雷斯）和转录因子的输入，调节Sp-kirrelL，包括直接，积极的输入，从两个关键的转录因子在骨骼生成GRN，Alx 1和Ets 1。接下来，我们确定了kirrelL顺式调控区从其他七个棘皮动物物种，共同代表所有类内的门。通过将这些异源调控区引入发育中的海胆胚胎，我们提供了它们在5亿年进化中显着保护的证据。我们详细解剖了海星星星Patiria miniata的kirrelL调控区，并证明它也接受来自Alx 1和Ets 1的直接输入。我们的研究结果确定kirrelL作为祖先棘皮动物骨骼GRN的组成部分。他们支持GRN子电路，包括特定的转录因子-CRE相互作用，可以在进化历史的漫长时期保持稳定的观点。最后，我们对kirrelL的分析建立了发育GRN和控制关键形态发生细胞行为（细胞-细胞融合）的效应基因之间的直接联系，为扩展GRN的解释力提供了一个范例。
The gene regulatory network (GRN) that underlies echinoderm skeletogenesis is a prominent model of GRN architecture and evolution. KirrelL is an essential downstream effector gene in this network and encodes an Ig-superfamily protein required for the fusion of skeletogenic cells and the formation of the skeleton. In this study, we dissected the transcriptional control region of the kirrelL gene of the purple sea urchin, Strongylocentrotus purpuratus. Using plasmid- and bacterial artificial chromosome-based transgenic reporter assays, we identified key cis-regulatory elements (CREs) and transcription factor inputs that regulate Sp-kirrelL, including direct, positive inputs from two key transcription factors in the skeletogenic GRN, Alx1 and Ets1. We next identified kirrelL cis-regulatory regions from seven other echinoderm species that together represent all classes within the phylum. By introducing these heterologous regulatory regions into developing sea urchin embryos we provide evidence of their remarkable conservation across ~500 million years of evolution. We dissected in detail the kirrelL regulatory region of the sea star, Patiria miniata, and demonstrated that it also receives direct inputs from Alx1 and Ets1. Our findings identify kirrelL as a component of the ancestral echinoderm skeletogenic GRN. They support the view that GRN subcircuits, including specific transcription factor–CRE interactions, can remain stable over vast periods of evolutionary history. Lastly, our analysis of kirrelL establishes direct linkages between a developmental GRN and an effector gene that controls a key morphogenetic cell behavior, cell–cell fusion, providing a paradigm for extending the explanatory power of GRNs.