A team of scientists from the Weizmann Institute, led by Prof. Talila Volk from the Department of Molecular Genetics, recently discovered how an intracellular control mechanism, which functions as a kind of "traffic policeman", stops the processes of cell division, and gives a "green light" to the processes of differentiation
Shortly after the fateful meeting between the sperm and egg, the fertilized cell begins a rapid process of division and reproduction. This creates a large number of identical cells. But in order for a normal fetus to develop, with functioning organs, these cells must differentiate and become cells of different tissues, such as muscles, nerves, blood cells, liver cells, and more. These two processes (culture and differentiation) cannot occur at the same time. The fetus must, somewhere, manage their "work arrangement", one by one. A team of scientists from the Weizmann Institute, led by Prof. Talila Volk from the Department of Molecular Genetics, recently discovered how an intracellular control mechanism, which functions as a kind of "traffic policeman", stops the processes of cell division, and gives a "green light" to the processes of differentiation. These findings were recently published in the scientific journal CURRENT BIOLOGY.
The scientists revealed a series of interactions between proteins, which controls the order of development processes in the first stages of the embryo's existence. One of the halo proteins, called HOW, is the "traffic cop" that directs and schedules the development and differentiation processes. This protein stops the RNA strands on their way to form a protein called Cdc25, which controls the timing of cell division. In fact, the formation of this protein is controlled by another protein, called Twist, which drives the whole process. In this script, which is performed in a precise and complex choreography, cells migrate from the outer layer of the tiny embryo to its inner region, differentiating as they go. These cells form the mesoderm - the intermediate layer - which will later turn into muscles and other internal tissues. At the same time, the protein Twist, which defines the mesoderm layer, stimulates the expression of the gene encoding the Cdc25 protein, and in addition, drives the production process of the HOW protein. At this point, HOW takes a decisive step and smashes into pieces the RNA on its way to produce Cdc25. As a result, cell division and proliferation are inhibited, which gives a "green light" to the differentiation of the embryonic cells and the formation of the mesoderm.
This research was carried out in mutant (genetically engineered) embryos of the fly "Drosophila melanogaster", which lacked the gene encoding the HOW protein. Prof. Wolk and the members of her research group found that in these embryos (how-deficient), severe defects occur in the timing and timing of the "change of shifts" between cell division and differentiation. In practice, the embryonic cells continued to divide excessively and the processes of movement and differentiation of the future mesoderm cells were delayed.
As soon as the creation of the mesoderm ends, the "traffic light changes" once more, and the cells start another journey of division and culture. The scientists believe that this exchange is due to the fact that, despite the extensive hunt that follows them, some single strands of RNA that encode the Cdc25 protein manage to escape the HOW policemen. Thus, the level of Cdc25 rises slowly, until it reaches the levels necessary for reactivation of the processes of cell division and reproduction. The scientists discovered that the increase in the level of Cdc25 takes place in a delicate and precise coordination, and it reaches the amount necessary to renew the processes of division and reproduction exactly when the cells complete the differentiation processes necessary for the formation of the mesoderm, and settle in the inner layer of the developing embryo.
Prof. Wolk and the members of her research group believe that the HOW protein plays other important roles in more advanced stages in the development of the mesoderm in the "Drosophila research" embryos. Similar proteins act in a similar way in the developing embryos of other animals, including mammals.
