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

1.

Imai KS, Levine M, Satoh N, Satou Y. Regulatory blueprint for a chordate embryo. Science. 2006; 312:

1183–1187. https://doi.org/10.1126/science.1123404 PMID: 16728634

2.

Satou Y. A gene regulatory network for cell fate specification in Ciona embryos. Current topics in developmental biology. 2020; 139: 1–33.

3.

Hudson C, Sirour C, Yasuo H. Co-expression of Foxa.a, Foxd and Fgf9/16/20 defines a transient

mesendoderm regulatory state in ascidian embryos. Elife. 2016; 5: e14692.

4.

Tokuhiro S, Satou Y. Cis-regulatory code for determining the action of Foxd as both an activator and a

repressor in ascidian embryos. Dev Biol. 2021; 476: 11–17. https://doi.org/10.1016/j.ydbio.2021.03.010

PMID: 33753082

5.

Tokuoka M, Maeda K, Kobayashi K, Mochizuki A, Satou Y. The gene regulatory system for specifying

germ layers in early embryos of the simple chordate. Sci Adv. 2021; 7: eabf8210. https://doi.org/10.

1126/sciadv.abf8210 PMID: 34108211

6.

Tokuoka M, Kobayashi K, Satou Y. Distinct regulation of Snail in two muscle lineages of the ascidian

embryo achieves temporal coordination of muscle development. Development. 2018; 145: dev163915.

7.

Imai KS, Hino K, Yagi K, Satoh N, Satou Y. Gene expression profiles of transcription factors and signaling molecules in the ascidian embryo: towards a comprehensive understanding of gene networks.

Development. 2004; 131: 4047–4058. https://doi.org/10.1242/dev.01270 PMID: 15269171

8.

Albert R, Othmer HG. The topology of the regulatory interactions predicts the expression pattern of the

segment polarity genes in Drosophila melanogaster. Journal of theoretical biology. 2003; 223: 1–18.

9.

Espinosa-soto C, Padilla-Longoria P, Alvarez-Buylla ER. A gene regulatory network model for cell-fate

determination during Arabidopsis thalianal flower development that is robust and recovers experimental

gene expression profiles. Plant Cell. 2004; 16: 2923–2939.

10.

Peter IS, Faure E, Davidson EH. Predictive computation of genomic logic processing functions in

embryonic development. Proc Natl Acad Sci U S A. 2012; 109: 16434–16442. https://doi.org/10.1073/

pnas.1207852109 PMID: 22927416

PLOS Genetics | https://doi.org/10.1371/journal.pgen.1010953 September 27, 2023

17 / 19

PLOS GENETICS

Robust buffers in gene regulation

11.

Sanchez L, Thieffry D. A logical analysis of the Drosophila gap-gene system. Journal of theoretical biology. 2001; 211: 115–141.

12.

Hudson C, Darras S, Caillol D, Yasuo H, Lemaire P. A conserved role for the MEK signalling pathway in

neural tissue specification and posteriorisation in the invertebrate chordate, the ascidian Ciona intestinalis. Development. 2003; 130: 147–159.

13.

Hudson C, Kawai N, Negishi T, Yasuo H. β-catenin-driven binary fate specification segregates germ

layers in ascidian embryos. Curr Biol. 2013; 23: 491–495.

14.

Imai KS, Hudson C, Oda-Ishii I, Yasuo H, Satou Y. Antagonism between β-catenin and Gata.a sequentially segregates the germ layers of ascidian embryos. Development. 2016; 143: 4167–4172.

15.

Kumano G, Takatori N, Negishi T, Takada T, Nishida H. A maternal factor unique to ascidians silences

the germline via binding to P-TEFb and RNAP II regulation. Curr Biol. 2011; 21: 1308–1313. https://doi.

org/10.1016/j.cub.2011.06.050 PMID: 21782435

16.

Oda-Ishii I, Abe T, Satou Y. Dynamics of two key maternal factors that initiate zygotic regulatory programs in ascidian embryos. Dev Biol. 2018; 437: 50–59. https://doi.org/10.1016/j.ydbio.2018.03.009

PMID: 29550363

17.

Oda-Ishii I, Kubo A, Kari W, Suzuki N, Rothbacher U, Satou Y. A maternal system initiating the zygotic

developmental program through combinatorial repression in the ascidian embryo. PLoS genetics. 2016;

12: e1006045. https://doi.org/10.1371/journal.pgen.1006045 PMID: 27152625

18.

Oda-Ishii I, Satou Y. Initiation of the zygotic genetic program in the ascidian embryo. Semin Cell Dev

Biol. 2018; 84: 111–117. https://doi.org/10.1016/j.semcdb.2018.02.012 PMID: 29438806

19.

Ohta N, Satou Y. Multiple signaling pathways coordinate to induce a threshold response in a chordate

embryo. PLoS genetics. 2013; 9: e1003818. https://doi.org/10.1371/journal.pgen.1003818 PMID:

24098142

20.

Ohta N, Waki K, Mochizuki A, Satou Y. A Boolean function for neural induction reveals a critical role of

direct intercellular interactions in patterning the ectoderm of the ascidian embryo. PLoS Comput Biol.

2015; 11: e1004687. https://doi.org/10.1371/journal.pcbi.1004687 PMID: 26714026

21.

Rothba¨cher U, Bertrand V, Lamy C, Lemaire P. A combinatorial code of maternal GATA, Ets and βcatenin-TCF transcription factors specifies and patterns the early ascidian ectoderm. Development.

2007; 134: 4023–4032.

22.

Shirae-Kurabayashi M, Matsuda K, Nakamura A. Ci-Pem-1 localizes to the nucleus and represses

somatic gene transcription in the germline of Ciona intestinalis embryos. Development. 2011; 138:

2871–2881.

23.

Tassy O, Daian F, Hudson C, Bertrand V, Lemaire P. A quantitative approach to the study of cell shapes

and interactions during early chordate embryogenesis. Curr Biol. 2006; 16: 345–358. https://doi.org/10.

1016/j.cub.2005.12.044 PMID: 16488868

24.

Yagi K, Satoh N, Satou Y. Identification of downstream genes of the ascidian muscle determinant gene

Ci-macho1. Dev Biol. 2004; 274: 478–489.

25.

Tsang AP, Visvader JE, Turner CA, Fujiwara Y, Yu CN, Weiss MJ, et al. FOG, a multitype zinc finger

protein, acts as a cofactor for transcription factor GATA-1 in erythroid and megakaryocytic differentiation. Cell. 1997; 90: 109–119. https://doi.org/10.1016/s0092-8674(00)80318-9 PMID: 9230307

26.

Bertrand V, Hudson C, Caillol D, Popovici C, Lemaire P. Neural tissue in ascidian embryos is induced

by FGF9/16/20, acting via a combination of maternal GATA and Ets transcription factors. Cell. 2003;

115: 615–627. https://doi.org/10.1016/s0092-8674(03)00928-0 PMID: 14651852

27.

Imai KS, Kobayashi K, Kari W, Rothbacher U, Ookubo N, Oda-Ishii I, et al. Gata is ubiquitously required

for the earliest zygotic gene transcription in the ascidian embryo. Dev Biol. 2020; 458: 215–227. https://

doi.org/10.1016/j.ydbio.2019.11.009 PMID: 31751550

28.

Hudson C, Yasuo H. Patterning across the ascidian neural plate by lateral Nodal signalling sources.

Development. 2005; 132: 1199–1210. https://doi.org/10.1242/dev.01688 PMID: 15750182

29.

Hudson C, Yasuo H. A signalling relay involving Nodal and Delta ligands acts during secondary notochord induction in Ciona embryos. Development. 2006; 133: 2855–2864.

30.

Hong JW, Hendrix DA, Levine MS. Shadow enhancers as a source of evolutionary novelty. Science.

2008; 321: 1314. https://doi.org/10.1126/science.1160631 PMID: 18772429

31.

Oda-Ishii I, Bertrand V, Matsuo I, Lemaire P, Saiga H. Making very similar embryos with divergent

genomes: conservation of regulatory mechanisms of Otx between the ascidians Halocynthia roretzi and

Ciona intestinalis. Development. 2005; 132: 1663–1674.

32.

Oudelaar AM, Higgs DR. The relationship between genome structure and function. Nature Reviews

Genetics. 2021; 22: 154–168. https://doi.org/10.1038/s41576-020-00303-x PMID: 33235358

PLOS Genetics | https://doi.org/10.1371/journal.pgen.1010953 September 27, 2023

18 / 19

PLOS GENETICS

Robust buffers in gene regulation

33.

Wittkopp PJ, Kalay G. Cis-regulatory elements: molecular mechanisms and evolutionary processes

underlying divergence. Nature Reviews Genetics. 2012; 13: 59–69.

34.

Yuh CH, Bolouri H, Davidson EH. Cis-regulatory logic in the endo16 gene: switching from a specification

to a differentiation mode of control. Development. 2001; 128: 617–629. https://doi.org/10.1242/dev.

128.5.617 PMID: 11171388

35.

Tokuhiro S, Tokuoka M, Kobayashi K, Kubo A, Oda-Ishii I, Satou Y. Differential gene expression along

the animal-vegetal axis in the ascidian embryo is maintained by a dual functional protein Foxd. PLoS

genetics. 2017; 13: e1006741. https://doi.org/10.1371/journal.pgen.1006741 PMID: 28520732

36.

Imai KS, Satou Y, Satoh N. Multiple functions of a Zic-like gene in the differentiation of notochord, central nervous system and muscle in Ciona savignyi embryos. Development. 2002; 129: 2723–2732.

37.

Yu D, Oda-Ishii I, Kubo A, Satou Y. The regulatory pathway from genes directly activated by maternal

factors to muscle structural genes in ascidian embryos. Development. 2019; 146: dev173104. https://

doi.org/10.1242/dev.173104 PMID: 30674480

38.

Khoueiry P, Rothbacher U, Ohtsuka Y, Daian F, Frangulian E, Roure A, et al. A cis-regulatory signature

in ascidians and flies, independent of transcription factor binding sites. Curr Biol. 2010; 20: 792–802.

https://doi.org/10.1016/j.cub.2010.03.063 PMID: 20434338

39.

Coulcher JF, Roure A, Chowdhury R, Robert M, Lescat L, Bouin A, et al. Conservation of peripheral nervous system formation mechanisms in divergent ascidian embryos. Elife. 2020; 9: e59157. https://doi.

org/10.7554/eLife.59157 PMID: 33191918

40.

Lowe EK, Stolfi A. Developmental system drift in motor ganglion patterning between distantly related

tunicates. Evodevo. 2018; 9: 18. https://doi.org/10.1186/s13227-018-0107-0 PMID: 30062003

41.

Satou Y, Kawashima T, Shoguchi E, Nakayama A, Satoh N. An integrated database of the ascidian,

Ciona intestinalis: Towards functional genomics. Zool Sci. 2005; 22: 837–843.

42.

Satou Y, Tokuoka M, Oda-Ishii I, Tokuhiro S, Ishida T, Liu B, et al. A Manually Curated Gene Model Set

for an Ascidian, Ciona robusta (Ciona intestinalis Type A). Zool Sci. 2022; 39: 253–260.

43.

Satou Y, Mineta K, Ogasawara M, Sasakura Y, Shoguchi E, Ueno K, et al. Improved genome assembly

and evidence-based global gene model set for the chordate Ciona intestinalis: new insight into intron

and operon populations. Genome Biol. 2008; 9: R152.

44.

Lemaire P, Garrett N, Gurdon JB. Expression cloning of Siamois, a Xenopus homeobox gene

expressed in dorsal-vegetal cells of blastulae and able to induce a complete secondary axis. Cell. 1995;

81: 85–94.

45.

Brinkman EK, Chen T, Amendola M, van Steensel B. Easy quantitative assessment of genome editing

by sequence trace decomposition. Nucleic Acids Res. 2014; 42: e168. https://doi.org/10.1093/nar/

gku936 PMID: 25300484

46.

Satou Y, Nakamura R, Yu D, Yoshida R, Hamada M, Fujie M, et al. A nearly complete genome of Ciona

intestinalis type A (C. robusta) reveals the contribution of inversion to chromosomal evolution in the

genus Ciona. Genome biology and evolution. 2019; 11: 3144–3157.

47.

Picco V, Hudson C, Yasuo H. Ephrin-Eph signalling drives the asymmetric division of notochord/neural

precursors in Ciona embryos. Development. 2007; 134: 1491–1497.

48.

Shi W, Levine M. Ephrin signaling establishes asymmetric cell fates in an endomesoderm lineage of the

Ciona embryo. Development. 2008; 135: 931–940.

PLOS Genetics | https://doi.org/10.1371/journal.pgen.1010953 September 27, 2023

19 / 19

...