At what stage do cells lose totipotency and form the primary germ layers?

During the development of an embryo, totipotency refers to the ability of a cell to differentiate into any type of cell needed for the organism, including both embryonic and extra-embryonic tissues. This level of differentiation is maintained in the earliest cells formed after fertilization, specifically in the zygote and the initial cleavage stages.

As development progresses, cells begin to lose their totipotency during the blastulation stage, where the formation of the blastocyst occurs. This is characterized by the differentiation of cells into two distinct groups: the inner cell mass, which will become the embryo itself, and the trophoblast, which will support implantation and form part of the placenta. Although the inner cell mass retains pluripotency (the ability to become any of the three primary germ layers), it is during this stage that cells start to lose the ability to form all cell types necessary for the entirety of the organism.

The next significant event in development is gastrulation, which is when the three primary germ layers—ectoderm, mesoderm, and endoderm—are formed. This further establishes the developmental pathway for all subsequent cell types. However, the initial loss of totipotency primarily occurs during blastulation, where the groundwork for