The heartbeat of the tiny mouse embryo is a sign that it is alive. The embryo's muscles, blood vessels and gut are all developing. This embryo is unique because it was created in a laboratory using mouse embryonic stem cell. It represents the most advanced in vitro (in-a-dish) mammal model ever made.This model was developed by Bernard and Christine Thisse at the University of Virginia School of Medicine. It is a significant step in scientists' efforts for stem cell-based mimicry of natural mammal development. It is a marvel that will allow scientists to better understand mammalian development and fight diseases."We discovered a way to instruct stem cells in aggregates to start embryonic development. Christine Thisse, PhD of UVA's Department of Cell Biology, explained that the controlled instruction causes the aggregates to develop into embryo-like entities. This process recapitulates all the embryonic stages one-by-one. It is incredible that we can obtain the same variety of tissues found in authentic mouse embryos.Bernard Thisse (Doctor of Cell Biology) also noted the importance of the breakthrough: "Human organs consist of multiple cell types that originated from different parts of a growing embryo," he stated. For example, the gut is made up of cells that form a hollow tube. These models are known as gut organoids. This tube alone is not sufficient to create a functional gut. It also contains other components such as smooth muscles and blood vessels. These organs are made of cells from different sources and control the function and functioning of the gut. It is impossible to create functional organs without all of the cells that are necessary for their formation. We have created embryo-like entities using stem cells. Stem Cells' PotentialStem cells can be transformed into special cell types that have specific functions. Stem cells can turn into other cell types with specific functions, such as our hearts, brains, bones and nerves. Scientists have long sought to harness stem cell potential to improve medical research and help patients. However, it has been extremely difficult to build complex models that can accommodate multiple cell types. It's much easier to control the formation of one cell type in a dish, than to orchestrate the development of an organism as in nature.This sophisticated model from The Thisses is notable. Researchers report that it is the first in vitro mammalian embryo model with so many stem cell-derived tissues. The most important thing is that these structures are organized around the notochord, the precursor to the vertebral columns, which is a key characteristic of vertebrate animal. The Thisses' model combines different cell types in a beautiful and precise way. This is a remarkable achievement.The Thisses and their collaborators had the challenge of overcoming some of the most difficult stem cell challenges. Previous models didn't develop correctly, weren't properly organized, or had other problems. These problems were solved by the Thisses using their knowledge in developmental biology and their previous work with cells from fish embryos (published at Science in 2014). This is how you see the beginnings of a mouse inside a dish that has properly organized cells and tissues. The Thisses' model shows that the notochord is present, and can be accounted for. The digestive tract develops and the heart beats. A nervous system forms with the formation of the neural tube, which is the first time it has been done in vitro."This in vitro mouse model demonstrates that we can induce cells to execute complex developmental programmes in the correct sequence of steps." Christine Thisse stated that all of the tissues have been created, which allows scientists to believe they can build organs with proper vascularization and innervation. This is crucial to one day be able to make functional human replacement organs in the dish. This would solve the problem of transplant shortages.The new model of the Thisses isn't complete and cannot be made into one. The brain's anterior portion is missing. The embryoids are still developing at the same time as the middle of a mouse embryo's gestation. Researchers have created sophisticated structures that mimic the development of an embryo in a mouse embryo. This is their real achievement. This is a significant breakthrough in their field and gives scientists greater control over stem cells.Bernard Thisse stated that the embryoids currently being produced lack the anterior brain domains. "However, the techniques that we have developed should allow us to manipulate molecular signaling that controls embryo formation. This should lead to the generation of embryo-like entities with all tissues and organs, including the anterior brain.Christine Thisse stated that the knowledge gained throughout our careers as developmental biologists was a foundation for this stem cell study. This was a huge leap for us but it showed that even if you have a solid idea it can be used across barriers and be used for other purposes. Students: While nothing is definitive, there are many opportunities to learn more and solve problems.She said, "Watching an embryo grow is amazing to see." "I feel fortunate that my work allowed me to learn about how vertebrate and invertebrate embryos develop. We were able, using these principles to create embryo formation in a dish using stem cell building blocks. Published findingsNature Communications published the findings of the Thisses and their collaborators in a scientific journal. Peng-FeiXu, Ricardo Moraes Borges and Jonathan Fillatre were part of the research team. They also included Christine Thisse, Tao Cheng and Bernard Thisse.The March of Dimes (grant 1-FY15-298), Jefferson Trust (FAAJ3199), and the University of Virginia supported the research. CNPq Brazil (200535/2014-5) supported Maraysa De Oliveira - Melo.###