An Ex vivo System to Study Cellular Dynamics Underlying Mouse Peri-implantation Development

Overview

Journal Dev Cell

Publisher Cell Press

Specialties Cell Biology
Reproductive Medicine

Date 2022 Jan 22

PMID 35063082

Authors

Takafumi Ichikawa

Hui Ting Zhang

Laura Panavaite

Anna Erzberger

Dimitri Fabreges

Rene Snajder

Adrian Wolny

Ekaterina Korotkevich

Nobuko Tsuchida-Straeten

Lars Hufnagel

Anna Kreshuk

Takashi Hiiragi

Affiliations

Soon will be listed here.

Abstract

Upon implantation, mammalian embryos undergo major morphogenesis and key developmental processes such as body axis specification and gastrulation. However, limited accessibility obscures the study of these crucial processes. Here, we develop an ex vivo Matrigel-collagen-based culture to recapitulate mouse development from E4.5 to E6.0. Our system not only recapitulates embryonic growth, axis initiation, and overall 3D architecture in 49% of the cases, but its compatibility with light-sheet microscopy also enables the study of cellular dynamics through automatic cell segmentation. We find that, upon implantation, release of the increasing tension in the polar trophectoderm is necessary for its constriction and invagination. The resulting extra-embryonic ectoderm plays a key role in growth, morphogenesis, and patterning of the neighboring epiblast, which subsequently gives rise to all embryonic tissues. This 3D ex vivo system thus offers unprecedented access to peri-implantation development for in toto monitoring, measurement, and spatiotemporally controlled perturbation, revealing a mechano-chemical interplay between extra-embryonic and embryonic tissues.

Citing Articles

Generation of transient totipotent blastomere-like stem cells by short-term high-dose Pladienolide B treatment.

Zhang W, An S, Hou S, He X, Xiang J, Yan H Sci China Life Sci. 2025; .

PMID: 40024996 DOI: 10.1007/s11427-024-2774-2.

Origin, fate and function of extraembryonic tissues during mammalian development.

Thowfeequ S, Hanna C, Srinivas S Nat Rev Mol Cell Biol. 2024; .

PMID: 39627419 DOI: 10.1038/s41580-024-00809-w.

Novel imaging and biophysical approaches to study tissue hydraulics in mammalian folliculogenesis.

Turley J, Leong K, Chan C Biophys Rev. 2024; 16(5):625-637.

PMID: 39618785 PMC: 11604877. DOI: 10.1007/s12551-024-01231-4.

Developing a Predictive Model for Metastatic Potential in Pancreatic Neuroendocrine Tumor.

Greenberg J, Shah Y, Ivanov N, Marshall T, Kulm S, Williams J J Clin Endocrinol Metab. 2024; 110(1):263-274.

PMID: 38817124 PMC: 11651689. DOI: 10.1210/clinem/dgae380.

A comprehensive review: synergizing stem cell and embryonic development knowledge in mouse and human integrated stem cell-based embryo models.

Dupont C Front Cell Dev Biol. 2024; 12:1386739.

PMID: 38715920 PMC: 11074781. DOI: 10.3389/fcell.2024.1386739.

References

Udan R, Piazza V, Hsu C, Hadjantonakis A, Dickinson M . Quantitative imaging of cell dynamics in mouse embryos using light-sheet microscopy. Development. 2014; 141(22):4406-14. PMC: 4302910. DOI: 10.1242/dev.111021. View

Beck S, Le Good J, Guzman M, Ben Haim N, Roy K, Beermann F . Extraembryonic proteases regulate Nodal signalling during gastrulation. Nat Cell Biol. 2002; 4(12):981-5. DOI: 10.1038/ncb890. View

Niwayama R, Moghe P, Liu Y, Fabreges D, Buchholz F, Piel M . A Tug-of-War between Cell Shape and Polarity Controls Division Orientation to Ensure Robust Patterning in the Mouse Blastocyst. Dev Cell. 2019; 51(5):564-574.e6. PMC: 6892278. DOI: 10.1016/j.devcel.2019.10.012. View

McDole K, Zheng Y . Generation and live imaging of an endogenous Cdx2 reporter mouse line. Genesis. 2012; 50(10):775-82. PMC: 3477249. DOI: 10.1002/dvg.22049. View

Martin A, Kaschube M, Wieschaus E . Pulsed contractions of an actin-myosin network drive apical constriction. Nature. 2008; 457(7228):495-9. PMC: 2822715. DOI: 10.1038/nature07522. View

Dumortier J, Le Verge-Serandour M, Tortorelli A, Mielke A, de Plater L, Turlier H . Hydraulic fracturing and active coarsening position the lumen of the mouse blastocyst. Science. 2019; 365(6452):465-468. DOI: 10.1126/science.aaw7709. View

Christodoulou N, Weberling A, Strathdee D, Anderson K, Timpson P, Zernicka-Goetz M . Morphogenesis of extra-embryonic tissues directs the remodelling of the mouse embryo at implantation. Nat Commun. 2019; 10(1):3557. PMC: 6686005. DOI: 10.1038/s41467-019-11482-5. View

Yue Y, Zong W, Li X, Li J, Zhang Y, Wu R . Long-term, in toto live imaging of cardiomyocyte behaviour during mouse ventricle chamber formation at single-cell resolution. Nat Cell Biol. 2020; 22(3):332-340. DOI: 10.1038/s41556-020-0475-2. View

Di-Gregorio A, Sancho M, Stuckey D, Crompton L, Godwin J, Mishina Y . BMP signalling inhibits premature neural differentiation in the mouse embryo. Development. 2007; 134(18):3359-69. DOI: 10.1242/dev.005967. View

10.

Chan C, Costanzo M, Ruiz-Herrero T, Monke G, Petrie R, Bergert M . Hydraulic control of mammalian embryo size and cell fate. Nature. 2019; 571(7763):112-116. DOI: 10.1038/s41586-019-1309-x. View

11.

Zhang Y, Conti M, Malide D, Dong F, Wang A, Shmist Y . Mouse models of MYH9-related disease: mutations in nonmuscle myosin II-A. Blood. 2011; 119(1):238-50. PMC: 3251230. DOI: 10.1182/blood-2011-06-358853. View

12.

Takaoka K, Yamamoto M, Hamada H . Origin and role of distal visceral endoderm, a group of cells that determines anterior-posterior polarity of the mouse embryo. Nat Cell Biol. 2011; 13(7):743-52. DOI: 10.1038/ncb2251. View

13.

Copp A . Interaction between inner cell mass and trophectoderm of the mouse blastocyst. II. The fate of the polar trophectoderm. J Embryol Exp Morphol. 1979; 51:109-20. View

14.

Warmflash A, Sorre B, Etoc F, Siggia E, Brivanlou A . A method to recapitulate early embryonic spatial patterning in human embryonic stem cells. Nat Methods. 2014; 11(8):847-54. PMC: 4341966. DOI: 10.1038/nmeth.3016. View

15.

Harland R, Gerhart J . Formation and function of Spemann's organizer. Annu Rev Cell Dev Biol. 1997; 13:611-67. DOI: 10.1146/annurev.cellbio.13.1.611. View

16.

Granier C, Gurchenkov V, Perea-Gomez A, Camus A, Ott S, Papanayotou C . Nodal cis-regulatory elements reveal epiblast and primitive endoderm heterogeneity in the peri-implantation mouse embryo. Dev Biol. 2010; 349(2):350-62. DOI: 10.1016/j.ydbio.2010.10.036. View

17.

Arnold S, Robertson E . Making a commitment: cell lineage allocation and axis patterning in the early mouse embryo. Nat Rev Mol Cell Biol. 2009; 10(2):91-103. DOI: 10.1038/nrm2618. View

18.

van den Brink S, Baillie-Johnson P, Balayo T, Hadjantonakis A, Nowotschin S, Turner D . Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells. Development. 2014; 141(22):4231-42. PMC: 4302915. DOI: 10.1242/dev.113001. View

19.

de Medeiros G, Kromm D, Balazs B, Norlin N, Gunther S, Izquierdo E . Cell and tissue manipulation with ultrashort infrared laser pulses in light-sheet microscopy. Sci Rep. 2020; 10(1):1942. PMC: 7005178. DOI: 10.1038/s41598-019-54349-x. View

20.

Ryan A, Chan C, Graner F, Hiiragi T . Lumen Expansion Facilitates Epiblast-Primitive Endoderm Fate Specification during Mouse Blastocyst Formation. Dev Cell. 2019; 51(6):684-697.e4. PMC: 6912163. DOI: 10.1016/j.devcel.2019.10.011. View