Synthetic mouse embryo could reduce the use of experimental animals

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International researchers have developed a synthetic, stem cell-derived mouse embryo which could reduce the need for experimental animals. The team developed the embryos using a combination of stem cells from mice. This synthetic embryo was able to copy the stages of mouse embryo development up to 8.5 days post-fertilisation and established all the brain regions, a neural tube, a beating heart, and a gut tube. In further experiments, the authors were able to demonstrate that disabling a gene called Pax6 - involved in the development of the eyes and other sensory organs - in their embryoid model resulted in similar effects to those seen in non-synthetic Pax6 diabled mouse embryos. The synthetic embryo can help understand factors that regulate the early stages of development, without the need for experimental animals, the authors say.

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From: Springer Nature

Developmental biology: Synthetic mouse embryos generated *UK SMC BRIEFING*

The generation of synthetic, stem cell-derived mouse embryos is described in a paper published in Nature this week. The embryo model copies the stages of natural mouse embryo development that take place up to day 8.5 post fertilization, including the establishment of defined regions of the brain, a neural tube and a beating heart-like structure. In addition, the model can replicate the consequences observed in natural mouse embryos from the knockout of a gene. The finding presents the possibility of using this model to understand factors that regulate the early stages of development, without the need for experimental animals.

Embryonic stem cells have the ability to form embryo-like structures in the laboratory. However, these models do not completely mimic all phases of development; for example, they do not fully recapitulate a process called neurulation (the formation of the neural tube, which will eventually differentiate into the brain and spinal cord).

Magdalena Zernicka-Goetz and colleagues assembled stem-cell derived mouse embryos in the laboratory using a combination of embryonic stem cells, trophoblast stem cells and inducible extraembryonic endoderm stem cells, all from mice. The resulting ETiX-embryoid model was able to develop beyond neurulation to the equivalent of 8.5 days post fertilization in a natural mouse embryo and established all the brain regions, a neural tube, a beating heart and a gut tube. The authors note that the model was able to achieve this through self-organization of the stem cell types, without the need for external signalling cues. In further experiments, the authors were able to demonstrate that knockout of the gene Pax6 — involved in the development of the eyes and other sensory organs — in their embryoid model resulted in similar effects to those seen in natural Pax6 knockout mouse embryos.

Zernicka-Goetz and co-authors conclude that the ETiX-embryoids provide a physiological relevant model of embryo development and present a new opportunity to study mechanisms of development and disease.

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conference:
Nature
Research:Paper
Organisation/s: University of Cambridge, UK
Funder: This project has been made possible through the following grants to MZG: NIH Pioneer Award (DP1 HD104575-01), European Research Council (669198), the Wellcome Trust (207415/Z/17/Z), Open Philanthropy/Silicon Valley Community Foundation and Weston Havens Foundation and the Centre for Trophoblast Research. FH was supported by the ERC (69566) and the Wellcome Trust (WT108438/C/15/Z); JdJ was supported by the Biotechnology and Biological Sciences Research Council. CEH was supported by the Centre for Trophoblast Research, and theLeventis Foundation. A grant from the Paul G. Allen Frontiers Group (Allen Discovery Centre for Cell Lineage Tracing) supported MZG, ME and JS. JS is also supported by the National Human Genome Research Institute (1UM1HG011586 to J.S.; R01HG010632 to J.S.) and is an Investigator of the Howard Hughes Medical Institute. HG is supported by a Biology and Biological Engineering postdoctoral fellowship from Caltech. DY is supported by a NIH-NRSA postdoctoral fellowship (5F32HD105442)
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