when I grow up

In the process of development and differentiation, embryonic stem cells find themselves at several such decision nodes. A developing embryo starts from one cell that divides into two cells, which divide into four cells, and so on. The future of each cell during embryonic development depends on a complex timing of molecular events ("decisions")


Dr. Eldad Tzhor. Fetal development

Life often places us at crossroads where we are required to make decisions. Every time we make such a decision, we choose for ourselves one path of development, and at the same time give up many possible paths, which we will no longer be able to return to. In the process of development and differentiation, embryonic stem cells find themselves at several such decision nodes. A developing embryo starts from one cell that divides into two cells, which divide into four cells, and so on. The future of each cell in the further development process of the embryo depends on a complex timing of molecular events ("decisions"), which are influenced, among other things, by the timing and order of the communication processes between the cells, as well as the degree of proximity of the cell that "makes the decision" to other cells. Embryonic cells in general, and stem cells in particular, are constantly changing, developing and differentiating. The molecular communication they maintain between them affects their development and their fate when they make a series of decisions that turn one cell, the fertilized egg, into billions of cells that divide into thousands of different cell types. In the earliest stages of embryonic development, the embryonic stem cell can choose for itself a developmental pathway from among a large number of possible pathways. Like a child who thinks about what he will be "when he grows up", and sees all the possibilities open before him, an embryonic stem cell can turn to development paths that will lead him, for example, to a "career" of a heart muscle cell, or a blood cell, or a nerve cell, or a skin cell , and many more diverse options. But with the open options also come the dangers:

Wrong decisions by these cells can cause significant health problems for the whole organism. For example, when cells that are supposed to develop, differentiate and form the heart muscle send wrong messages between them, this can lead to congenital heart diseases. The scientists believe that if we understand the normal developmental pathways of embryonic cells, we may be able to correct or even prevent the mistakes before they develop and cause diseases. This ambition is the driving force behind studies designed to find ways to influence the "decision-making" of embryonic cells, and in this way direct them to certain development and differentiation pathways. Dr. Eldad Tzhor from the Department of Biological Control at the Weizmann Institute of Science, and the members of the research group he heads, aim to identify the series of events that occur during normal embryonic development leading to the formation of a heart or muscle tissue. To this end, they are conducting a series of studies in chicken embryos. The chicken embryo is particularly suitable For this study, because it is easy to grow in laboratory conditions, its development lasts a relatively short time (only 21 days), and because in the first stages of development there are no significant differences between the embryos of the chicken and other vertebrates, including humans The chicken can be used as a suitable model for studying the processes that can cause birth defects in humans. The size of the embryo and its accessibility allow researchers to intervene in its development processes, and to examine the results of the intervention. This way, it is possible, for example, to simulate various disorders in the development process and to examine new ways of correcting these disorders. Dr. Tzhor cells from a chicken embryo, and examined the developmental pathway that was supposed to lead them to differentiate into muscle tissue. But to his surprise, the differentiated cells became beating heart cells. Dr. Tzhor: "It turns out that cells that normally do not differentiate into heart muscle cells, may sometimes, nevertheless, become heart cells. This phenomenon takes place when these cells develop and differentiate in an environment different from their original environment." Later, Dr. Tzhor discovered one pathway of intercellular molecular communication, called TNW, whose activity prevents the cells of the embryo from becoming heart cells. This pathway is based on chemical communication signals that reach the cell, and activate in it a chain of chemical message transmission, which reaches the cell nucleus and activates various genes whose proteins they produce change the behavior of the cell. In his current research, Dr. Tzhor strives to discover additional communication pathways that inhibit differentiation, as well as pathways that encourage the differentiation of embryonic cells into heart cells. for each type of cell, and to create different tissues, may allow "patching" of different tissues, such as heart tissue damaged as a result of a heart attack. This tissue is not able to recover and does not grow again. Therefore, "reinforcement" in the form of stem cells that will differentiate into heart cells "The missing lines," may constitute an effective and unique way of treatment that currently has no known substitute. "It turns out that the cells need to walk side by side and talk to each other so that they can make the right decisions, which ultimately lead to separate ways of development," says D. R Tzhor "The molecular communication between the cells enables the perfect timing of the events in the process of fetal development. We strive to understand the language in which this communication takes place. To understand the development process of the heart, for example, we need to ask the most basic questions, and find and develop new ways that will allow for us to examine particularly dynamic and complex processes of fetal development."

personal

Eldad Tzhor grew up in Kibbutz Maoz Haim, where he worked in a dairy farm, also took care of horses, and learned closely about the cycles of life. After military service in the "Golani" division, studies for a bachelor's degree in the Faculty of Agriculture of the Hebrew University, and a trip that lasted about a year in South America, he began his doctoral studies at the Feinberg Seminary of the Weizmann Institute of Science, in the laboratory of Prof. Yosef Jordan, then in the Department of Molecular Biology of the Cell.

In 1998, he began post-doctoral research in the Department of Biological Chemistry and Molecular Pharmacology of the Harvard Medical School. In 2003 he returned to Israel, and joined the Department of Biological Control at the Weizmann Institute of Science as a senior researcher. Eldad Tzhor is married to Talia and has two children, Noam (nine years old) and Roy (four years old).

the heart of the matter

The heart pumps five and a half liters of blood, three times a minute, and circulates them throughout the body. Even when we sleep, the heart muscles work twice as hard as the leg muscles of a runner. The heart is the first organ to develop in the fetus, and it continues to beat from the first beat until the end of life, an average of more than two and a half billion times. Development, differentiation and cancer The types of decisions made by embryonic stem cells in the differentiation process are somewhat similar to the decisions made by adult cells, which may turn them into cancer cells. Here, too, life and death are in the hands of molecular communication.

Communication signals with the wrong strength, at the wrong time, may cause the cell to make wrong decisions. For example, when an adult cell mistakenly decides to continue multiplying, as if it were still an embryonic cell, it actually causes the development of a potentially fatal cancerous tumor. In other words, it's all about timing. Culture is a desirable process in embryonic tissue, but highly undesirable in mature tissue. A better understanding of the molecular communication that causes this fateful decision may, perhaps, in the future, offer new ways to prevent the development of cancerous tumors.

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