{"title":"极性建立和不依赖于中心纵轴的细胞分裂的最小数学模型","authors":"O. Maxian, Katrina M Longhini, M. Glotzer","doi":"10.1101/2024.08.07.607072","DOIUrl":null,"url":null,"abstract":"The anterior-posterior axis of Caenorhabditis elegans embryos is determined by the position of sperm entry. The sperm-provided centrosome induces local inhibition of cortical contractility, leading to large-scale myosin flows. This process is driven by the guanine nucleotide exchange factor (GEF) ECT-2, which activates myosin through the GTPase RHO-1. Previously, we showed that in both cell polarization and cytokinesis, Aurora A (AIR-1) is activated on the centrosomes and diffuses to the cortex, where it locally inhibits ECT-2, leading to gradients in myosin concentration. These gradients in turn drive long-range flows that amplify ECT-2 asymmetries (Longhini and Glotzer, 2022). Here, we construct a mathematical model to test whether a minimal set of well characterized, essential elements are necessary and sufficient to explain the spatiotemporal dynamics of AIR-1, ECT-2, and myosin during polarization of the C. elegans model organism. We show that robust establishment of polarity can be obtained in response to a weak AIR-1 signal, and demonstrate the relevance of rapid ECT-2 exchange and a persistent AIR-1 cue during polarization. The tuned model also correctly predicts previously-observed ultrasensitive ECT-2 dynamics during cytokinesis, suggesting that the same minimal circuit operates in both processes.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A minimal mathematical model for polarity establishment and centralsplindlin-independent cytokinesis\",\"authors\":\"O. Maxian, Katrina M Longhini, M. Glotzer\",\"doi\":\"10.1101/2024.08.07.607072\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"The anterior-posterior axis of Caenorhabditis elegans embryos is determined by the position of sperm entry. The sperm-provided centrosome induces local inhibition of cortical contractility, leading to large-scale myosin flows. This process is driven by the guanine nucleotide exchange factor (GEF) ECT-2, which activates myosin through the GTPase RHO-1. Previously, we showed that in both cell polarization and cytokinesis, Aurora A (AIR-1) is activated on the centrosomes and diffuses to the cortex, where it locally inhibits ECT-2, leading to gradients in myosin concentration. These gradients in turn drive long-range flows that amplify ECT-2 asymmetries (Longhini and Glotzer, 2022). Here, we construct a mathematical model to test whether a minimal set of well characterized, essential elements are necessary and sufficient to explain the spatiotemporal dynamics of AIR-1, ECT-2, and myosin during polarization of the C. elegans model organism. We show that robust establishment of polarity can be obtained in response to a weak AIR-1 signal, and demonstrate the relevance of rapid ECT-2 exchange and a persistent AIR-1 cue during polarization. The tuned model also correctly predicts previously-observed ultrasensitive ECT-2 dynamics during cytokinesis, suggesting that the same minimal circuit operates in both processes.\",\"PeriodicalId\":505198,\"journal\":{\"name\":\"bioRxiv\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-08-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"bioRxiv\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1101/2024.08.07.607072\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"bioRxiv","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2024.08.07.607072","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
A minimal mathematical model for polarity establishment and centralsplindlin-independent cytokinesis
The anterior-posterior axis of Caenorhabditis elegans embryos is determined by the position of sperm entry. The sperm-provided centrosome induces local inhibition of cortical contractility, leading to large-scale myosin flows. This process is driven by the guanine nucleotide exchange factor (GEF) ECT-2, which activates myosin through the GTPase RHO-1. Previously, we showed that in both cell polarization and cytokinesis, Aurora A (AIR-1) is activated on the centrosomes and diffuses to the cortex, where it locally inhibits ECT-2, leading to gradients in myosin concentration. These gradients in turn drive long-range flows that amplify ECT-2 asymmetries (Longhini and Glotzer, 2022). Here, we construct a mathematical model to test whether a minimal set of well characterized, essential elements are necessary and sufficient to explain the spatiotemporal dynamics of AIR-1, ECT-2, and myosin during polarization of the C. elegans model organism. We show that robust establishment of polarity can be obtained in response to a weak AIR-1 signal, and demonstrate the relevance of rapid ECT-2 exchange and a persistent AIR-1 cue during polarization. The tuned model also correctly predicts previously-observed ultrasensitive ECT-2 dynamics during cytokinesis, suggesting that the same minimal circuit operates in both processes.