A digital twin reproducing gene regulatory network dynamics of early Ciona embryos indicates robust buffers in the network

How gene regulatory networks (GRNs) encode gene expression dynamics and how GRNs evolve are not well understood, although these problems have been studied extensively. We created a digital twin that accurately reproduces expression dynamics of 13 genes that initiate expression in 32-cell ascidian embryos. We first showed that gene expression patterns can be manipulated according to predictions by this digital model. Next, to simulate GRN rewiring, we changed regulatory functions that represented their regulatory mechanisms in the digital twin, and found that in 55 of 100 cases, removal of a single regulator from a conjunctive clause of Boolean functions did not theoretically alter qualitative expression patterns of these genes. In other words, we found that more than half the regulators gave theoretically redundant temporal or spatial information to target genes. We experimentally substantiated that the expression pattern of Nodal was maintained without one of these factors, Zfpm, by changing the upstream regulatory sequence of Nodal. Such robust buffers of regulatory mechanisms may provide a basis of enabling developmental system drift, or rewiring of GRNs without changing expression patterns of downstream genes, during evolution

A bHLH transcription factor gene, Twist-like1, is essential for the formation of mesodermal tissues of Ciona juveniles

AbstractAscidian larval mesenchyme cells, comprising about 900 cells, are derived from the A7.6, B8.5 and B7.7 blastomere pairs in the 110-cell embryo. Previous studies showed that the properties of mesenchyme cells are not uniform among the three lines in embryos of Ciona savignyi and Ciona intestinalis. After metamorphosis, the larval mesenchyme cells form the mesodermal tissues or organs of the adult body. In the present study, the developmental fates of A7.6-, B8.5- and B7.7-line mesenchyme cells were traced using DiI to determine the origins of juvenile mesodermal tissues of C. savignyi. It was demonstrated that each of the A7.6-, B8.5- and B7.7-line mesenchyme cells is distributed in different positions of the larval trunk, and then give rise to the different mesodermal tissues of juveniles. Twist-like1 is a transcription factor gene essential for the specification of larval mesenchyme cells. Knockdown of this gene with specific morpholino antisense oligonucleotides affected not only the specification of larval mesenchyme cells, but also the formation of most of the mesodermal tissues of juveniles. The juvenile mesodermal tissues in the Twist-like1-knockdown specimen were never compensated by the surrounding tissues. The present results therefore indicate that Twist-like1 is required for the differentiation of most mesodermal precursors of adults

The gene regulatory system for specifying germ layers in early embryos of the simple chordate

動物胚の遺伝子発現を数式で表現 --動物の胚葉形成システムをまるごと理解--.京都大学プレスリリース. 2021-06-10.In animal embryos, gene regulatory networks control the dynamics of gene expression in cells and coordinate such dynamics among cells. In ascidian embryos, gene expression dynamics have been dissected at the single-cell resolution. Here, we revealed mathematical functions that represent the regulatory logics of all regulatory genes expressed at the 32-cell stage when the germ layers are largely specified. These functions collectively explain the entire mechanism by which gene expression dynamics are controlled coordinately in early embryos. We found that regulatory functions for genes expressed in each of the specific lineages contain a common core regulatory mechanism. Last, we showed that the expression of the regulatory genes became reproducible by calculation and controllable by experimental manipulations. Thus, these regulatory functions represent an architectural design for the germ layer specification of this chordate and provide a platform for simulations and experiments to understand the operating principles of gene regulatory networks

Using linkage logic theory to control dynamics of a gene regulatory network of a chordate embryo.

Linkage logic theory provides a mathematical criterion to control network dynamics by manipulating activities of a subset of network nodes, which are collectively called a feedback vertex set (FVS). Because many biological functions emerge from dynamics of biological networks, this theory provides a promising tool for controlling biological functions. By manipulating the activity of FVS molecules identified in a gene regulatory network (GRN) for fate specification of seven tissues in ascidian embryos, we previously succeeded in reproducing six of the seven cell types. Simultaneously, we discovered that the experimentally reconstituted GRN lacked information sufficient to reproduce muscle cells. Here, we utilized linkage logic theory as a tool to find missing edges in the GRN. Then, we identified a FVS from an updated version of the GRN and confirmed that manipulating the activity of this FVS was sufficient to induce all seven cell types, even in a multi-cellular environment. Thus, linkage logic theory provides tools to find missing edges in experimentally reconstituted networks, to determine whether reconstituted networks contain sufficient information to fulfil expected functions, and to reprogram cell fate

Controlling Cell Fate Specification System by Key Genes Determined from Network Structure

遺伝子ネットワークを制御してさまざまな種類の細胞を作り出す --数学的理論に基づく細胞運命の制御に成功--. 京都大学プレスリリース. 2018-06-13.Network structures describing regulation between biomolecules have been determined in many biological systems. Dynamics of molecular activities based on such networks are considered to be the origin of many biological functions. Recently, it has been proved mathematically that key nodes for controlling dynamics in networks are identified from network structure alone. Here, we applied this theory to a gene regulatory network for the cell fate specification of seven tissues in the ascidian embryo and found that this network, which consisted of 92 factors, had five key molecules. By controlling the activities of these key molecules, the specific gene expression of six of seven tissues observed in the embryo was successfully reproduced. Since this method is applicable to all nonlinear dynamic systems, we propose this method as a tool for controlling gene regulatory networks and reprogramming cell fates

Enrichment of Education and Research at Hiroshima University through the Top Global University Initiative: EBPM and Quality Assurance

Hiroshima University named its Super (Top) Global University Initiative the “Hiroshima University Global Campus Expansion and Innovation Initiative”. The Initiative is implemented as a university-wide project in which all faculties and departments are implicated in the pursuit of its goals. In this process, Hiroshima University collected extensive information on the educational, research and social contributions of the university, and made policy decisions on the basis of this objective data. In addition, Hiroshima University developed a system to monitor the achievements of the top 100 universities by developing its own KPIs, and a system that optimally allocates education and research resources. In this book, we review various aspects of Hiroshima University’s Super (Top) Global University Initiative. Part 1 focuses on its unique approaches related to IR and EBPM. In Part 2, we examine various education programmes and consider the implementation of the Initiative.はしがき… 西谷 元 i 第一部 教育・研究基盤の分析・目標設定・改革 第1章 広島大学の目標達成型重要業績指標AKPI®と教員エフォート指標BKPI®… 相田 美砂子 1 第2章 国際的な教育質保証に向けた取り組み（続編）… 渡邉 聡・村澤 昌崇・安部 保海・梅下 健一郎・中尾 走 11 第3章 BEVI を用いた留学効果の客観的測定 －客観的データに基づく留学プログラムの質保証－… 西谷 元 39 第4章 EBPM に基づく学生の英語運用能力の向上 －エビデンスに基づく教育プログラムの改革・実施・成果－… 西谷 元 53 第二部 国際標準の教育の提供 第5章 広島大学森戸国際高等教育学院とその新たな取組み… 荒見 泰史 67 第6章 三階層ティーチング・アシスタント制度「Hirodai TA」の展開 －多様性を保証するグローバル・バリアフリー・キャンパス構想に向けた成果と課題－… 丸山 恭司・佐藤 万知・河本 尚枝・島津 礼子・小澤 郁美・Simona Zollet 87 第7章 グローバル・キャンパスで学ぶ ―総合科学部国際共創学科の取組みと課題… 柴田 美紀・フンク カロリン 105 第8章 Global Peace Leadership Program… 小澤 孝一郎 12

Extending the Southern Shore of the Island of Inversion to F-28

Detailed spectroscopy of the neutron-unbound nucleus F-28 has been performed for the first time following proton/neutron removal from Ne-29/F-29 beams at energies around 230 MeV=nucleon. The invariant-mass spectra were reconstructed for both the F-27((*)) + n and F-26((*)) + 2n coincidences and revealed a series of well-defined resonances. A near-threshold state was observed in both reactions and is identified as the F-28 ground state, with S-n(F-28) = -199(6) keV, while analysis of the 2n decay channel allowed a considerably improved S-n(F-27) = 1620(60) keV to be deduced. Comparison with shell-model predictions and eikonal-model reaction calculations have allowed spin-parity assignments to be proposed for some of the lower-lying levels of F-28. Importantly, in the case of the ground state, the reconstructed F-27 + n momentum distribution following neutron removal from F-29 indicates that it arises mainly from the 1p(3/2) neutron intruder configuration. This demonstrates that the island of inversion around N = 20 includes F-28, and most probably F-29, and suggests that O-28 is not doubly magic