How do the embryonic brain cells know what they want - or need - to be, when they grow up?

The brains of zebrafish contain only a few tens of dopamine-producing neurons (compared to hundreds of thousands of cells in the human brain), which makes it possible to study processes that occur in individual cells

How do the embryonic brain cells know what they want - or need - to be, when they grow up? Scientists who seek to understand how a formless mass of embryonic cells develops and turns into the complex and elaborate structure called the "human brain", stand before a "black box": the development of the embryonic brain is hidden from view, hidden, among other things, behind the fetal skull and the mother's womb. Therefore, researchers turn to and learn about these processes using other creatures. "The zebrafish is an excellent model," says Dr. Gil Lebkowitz from the department of molecular cell biology at the Weizmann Institute of Science. "This is a vertebrate animal - like us,

Humans. However, a zebrafish embryo develops in a transparent egg, outside the mother's body, so that the brain cells can be observed through a microscope as they take shape." Dr. Lebkowitz investigates how the brain is formed, how its parts are shaped, and how the different nerve cells acquire their identity with the help of genetic methods that allow him to intervene in the molecular processes that occur in the embryonic cells. The "Factory" for fish eggs in his laboratory produces a variety of mutant fish, through which he examines and identifies genes and molecules that play central roles in brain development processes. In addition, cell and protein labeling methods allow scientists to track brain development in real time using a fluorescence microscope. "We monitor in five dimensions: length, width, depth, the time dimension, and a fifth dimension that refers to different types of cells and the areas in which they develop - which we mark with different colors using fluorescent proteins that are inserted into the genome using genetic methods," says Dr. Lebkowitz.

Dr. Lebkowitz's research focuses on the embryonic development (differentiation) of nerve cells in the brain that produce different types of neurotransmitters. In a study recently published in the scientific journal Development, Dr. Lebkowitz and his group members focused on the cells that produce dopamine - a neurotransmitter that plays an important role in the mechanisms of a sense of satisfaction (and is therefore also involved in addictions), and in motor and emotional activity. Abnormal activity of the system responsible for the production and use of dopamine can cause diseases such as Parkinson's and schizophrenia. The brains of zebrafish contain only a few tens of dopamine-producing neurons (compared to hundreds of thousands of cells in the human brain), which makes it possible to study processes that take place in individual cells that perform specific tasks. Dr. Lebkowitz is trying to understand what determines the number of dopamine-producing cells. He got the first clue to the answer in his post-doctoral research. Then he discovered that damage to a certain gene, called fezl, reduces the number of dopamine-secreting cells in the fish's brain.

In the current study, in which the research students Niva Rusk-Bloom and Amos Gutnik participated, together with Dr. Helit Navel-Rosen and Dr. Jeanne Lachman, as well as researchers from King's College London and the University of Utah, the scientists scanned a series of genes that participate in the design of various structures in the brain , and check whether they affect the number of dopamine-producing cells. This is how they discovered that inhibiting the activity of a protein called Wnt, known to be involved in normal developmental processes and in the development of cancerous tumors, increases the number of dopamine-producing cells. It was also found that Wnt supervises the activity of the known factor, Fezl. "So we currently know of two factors, one increases the number of cells and the other decreases it, and it is the balance between them that determines the exact number of cells," says Dr. Lebkowitz. "However, we still do not fully understand the mechanism, and as of today, we are looking for additional molecules and genes that are involved in the process."

The scientists were also able to locate the exact location in the embryonic region that contains the neural stem cells from which the dopamine-producing cells are formed and develop. It turns out that the exact number of these cells is determined at a much earlier embryonic stage than was commonly thought until now. Research aimed at developing future methods for the treatment of neurodegenerative diseases, such as Parkinson's, is based on attempts to transplant new neural stem cells into the brains of patients. Therefore, Dr. Lebkowitz believes that understanding the embryonic mechanisms that control the creation of dopamine-producing nerve cells may help treat people suffering from this type of nerve cell degeneration, such as patients with Parkinson's disease.

In short: the question: what determines the number of dopamine-producing cells in the brain during embryonic development?
The findings: The exact place where the dopamine-producing cells are formed was located, and it was discovered that inhibiting the activity of a certain protein increases their number.