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New Advance Supports Extended Ex Vivo Mouse Embryo Development

Review of "Ex utero mouse embryogenesis from pre-gastrulation to late organogenesis" from Nature by Stuart P. Atkinson

The development of optimized in vitro culture conditions that support the long-term development of post-implantation mouse embryos would allow a better understanding of the developmental processes that occur from pre-gastrulation to organogenesis [1]. Given that previously reported platforms suffered from significant limitations [2, 3], researchers led by Alejandro Aguilera-Castrejon, Rada Massarwa, Noa Novershtern, Jacob H. Hanna (Weizmann Institute of Science, Rehovot), and Itay Maza (Israel Institute of Technology - Technion, Haifa, Israel) focused on the development of a platform for the ex vivo culture of post-implantation mouse embryos that permitted the study of embryonic stages from before gastrulation till the hindlimb formation stage.

As reported in their recent study [4], Aguilera-Castrejon and Oldak et al. described detailed conditions for the ex vivo growth of mouse embryos from different stages using a customized electronic gas regulation module and optimized growth media. A static platform supported the culture of pre-gastrulation stage embryos (E5.5 or E6.5), while a three-dimensional rotating bottle culture platform supported the growth of late-gastrulating embryos (E7.5); however, the authors also demonstrated the ability to bridge ex vivo mouse pre-gastrulation development to advanced organogenesis by combining the static and roller culture protocols.

This new protocol supported the ex vivo growth of mouse embryos capable of proper symmetry breaking, the establishment of the germ layers and embryonic axis, and the differentiation and patterning of tissues and organs without maternal interaction over a period of six days. Furthermore, the described culture systems supported the application and monitoring of external and internal perturbations/micro-manipulations (e.g., genetic modification, chemical screens, tissue manipulation, and microscopy methods) whose impacts could be monitored ex vivo for up to six days.

Overall, the authors hope that their newly described platforms will support ongoing research into post-implantation morphogenesis and artificial embryogenesis in mammals by eliminating the uterine barrier and set the stage for research using different mammalian species and stem cell-aggregated synthetic embryos [5].

For more on this exciting new advance in ex vivo embryogenesis, stay tuned to the Stem Cells Portal!


  1. Tam PP, Postimplantation mouse development: whole embryo culture and micro-manipulation. International Journal of Developmental Biology 1998;42:895-902.
  2. Beddington RS, Induction of a second neural axis by the mouse node. Development 1994;120:613-20.
  3. Parameswaran M and Tam PPL, Regionalisation of cell fate and morphogenetic movement of the mesoderm during mouse gastrulation. Developmental Genetics 1995;17:16-28.
  4. Aguilera-Castrejon A, Oldak B, Shani T, et al., Ex utero mouse embryogenesis from pre-gastrulation to late organogenesis. Nature 2021;593:119-124.
  5. Harrison SE, Sozen B, Christodoulou N, et al., Assembly of embryonic and extraembryonic stem cells to mimic embryogenesis in vitro. Science 2017;356:eaal1810.