When a sperm fuses with an egg, a single-celled embryo is formed. As the embryo starts to divide, first into 2 cells and then 4, 8, 16 and so on, the cell number doubles each time, at this stage the embryo is simply a ball of identical-looking cells.
At approximately day 3 in the mouse embryo, the cells form into a morula, and at day 4-5 they form a blastocyst.
The blastocyst that is formed after 4-5 days of gestation now contains some clearly defined cell types. The cells in the outer layer will form the cells of the placenta, inside these cells there is a fluid-filled space with a ball of cells called the inner cell mass.
Cells from the inner cell mass are those that will give rise to the whole baby mouse. These cells are special because they have not yet specialised into one specific cell type, such as blood cells, skin cells or brain cells. The process of specialisation is known as differentiation. At Children’s Medical Research Institute (CMRI) we focus on understanding how these cells in the mouse embryo differentiate.
We have over 200 different cell types in our body, and these cells have very different functions. Just consider the role of muscle cells, nerve cells and skin cells. By the time we are born, our body is made up of trillions of cells.
Embryologists are interested in all aspects of the developmental processes before birth. Our research is important as it allows us not only to understand development but also to understand what goes wrong in birth defects.
Genes carry the information necessary to make proteins in the body. Genes are regulated, or controlled, so that they produce the right amount of protein, in the right part of the body, and at the right time. The regulation of these genes is particularly important in the developing embryo, where genes are “switched on” and “off” in a very precise manner. As an example, genes that produce proteins important for limb development need to be “switched on” during the right stage of development and in the tissues that are destined to form the limbs.
In the Embryology Unit
, CMRI scientists have identified a single gene defect that can cause cleft palate. When expression of the gene Pdgfc is “switched off” in mouse embryos, the embryos develop a number of abnormalities, the most significant being a cleft palate, which occurs in nearly 100% of cases.
In a family of several members with cleft palate, the PDGFC gene was found to be non-functional. A mutation was discovered in the promoter of the PDGFC gene. The mutation may cause a problem in “switching on” the gene and thus affects the production of PDGFC protein.
Scientists in the CMRI Embryology Unit are world leaders in fate mapping. They have drawn a map that shows where the cells of the embryo move to during development and what kind of specialised cells they eventually become in the baby and fully grown adult mouse.
An embryo has three layers; the ectoderm, mesoderm and endoderm. Cells of the ectoderm develop into organs such as the brain and spinal cord, cells of the mesoderm develop into tissues such as muscle and bone.
Over the past years, CMRI researchers have made a map of the ectoderm and mesoderm, they are currently looking at the more difficult endoderm layer, a single layer of cells that develop into the gut and other organs such as the pancreas, liver, thyroid and lungs.
Germ cells, the cells that will make up the eggs or the sperm of an individual know their fate from the first few days of life. However, during development they move from their point of origin and hide out near the gut where they wait for the developing ovary or testes to form.
Scientists believe this migration is to enable the germ cells to retain special “stem cell-like” properties, which are important to these unique cells. If they did not migrate, much of the embryo is undergoing extensive remodelling, and differentiation of neighbouring cells could affect the differentiation of these cells.
Two genes (IFITM1 and IFITM3), have been shown by scientists at CMRI to be essential for navigation of the germ cells through the embryo. When both genes are expressed, the cells remain at their point of origin. If IFITM1 is “switched off” and no longer expresses the protein, the cells are repelled from the point of origin and hide next to the gut. When this gene is switched back on the cells can take up residence in the newly formed ovary or testes. By “throwing the switch on and off” for this gene, the cells are guided into the right place.