Developmental genetics: how germ cells cut their parents' cord

Developmental genetics: how germ cells cut their parents’ cord


image: An adult specimen of the worm C. elegans and an embryo are shown. In the adult worm, the BCC-1 protein was labeled with a fluorescent protein (GFP) to monitor its activity.
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Credit: Uni Halle / AG Christian Eckmann

For the first cell to develop into an entire organism, genes, RNA molecules and proteins must work together in complex ways. At first, this process is indirectly controlled by the mother. At some point, the GRIF-1 protein causes the offspring to cut themselves off from this influence and begin their own development. A research team from Martin Luther University Halle-Wittenberg (MLU) details how this process works in the journal Scientists progress.

When a new organism begins to develop, the mother decides. During fertilization, the egg and sperm fuse together to form a single new cell. However, the course of cell division, and therefore the formation of a new living being, is initially determined by the mother cell. “In any organism, cell division is initially pre-programmed by the mother,” says geneticist Professor Christian Eckmann of MLU. The mother cell provides a developmental starter set that includes early proteins as well as RNA molecules that serve as templates for other proteins. All of this is necessary to restart cell division and the development of an organism.

During this initial period, the cell does not have access to its own genetic material, which limits its own development. “As important as this maternal contribution is for the new organism, at some point these components must be removed. Only then can it fully utilize its own genetic material and continue its own development,” says Eckmann. . This process begins much later in germ cells, the precursors of gametes, than in somatic cells, which develop into all other cells in the body. “Cells have a lot of options for killing things. Longevity has to be earned,” says Eckmann. In germ cell precursors, so-called poly-A polymerases provide the mother’s short-lived RNA molecules with a sort of protective cap to ensure they live longer.

In experiments with the model organism C.elegans, Eckmann’s team discovered how the cord-cutting process works at the molecular level in germ cells. At a certain stage, the cells begin to produce the GRIF-1 protein. Instructions for this process come from maternal RNA. As soon as the protein is built, it starts looking for the maternal poly-A polymerases, binds to them, and attaches some sort of tag to them. “It’s like a flag that GRIF-1 uses to mark which maternal proteins need to be degraded,” Eckmann explains. This sets off a chain reaction: once the poly-A polymerases are destroyed, they can no longer attach new protective caps to the maternal RNA molecules, which would protect them from degradation and thus no new maternal proteins can be built. . “Ultimately, all maternal RNA molecules and proteins are eliminated. The germ cell gets full access to its genetic material and can continue to develop on its own,” concludes Eckmann. It is still unclear how the cell knows to produce GRIF-1 and to activate its own genetic material.

Incidentally, this long process of maternal control exists for a reason: genetic material from germ cells is passed on to offspring via sperm or egg. Therefore, it should be kept as completely and error-free as possible. Eckmann researchers artificially prevented this degradation process from occurring in the laboratory in C.elegans. “A disruption of this process causes a lot of problems. The germline cannot develop robustly, and the worms’ offspring become more sterile with each generation,” says Eckmann.

The work was supported by the German Research Foundation as part of the research training group “GRK 2467: Intrinsically disordered proteins – Molecular principles, cellular functions and diseases”.

Study: Oyewale TD, Eckmann CR Germline immortality relies on TRIM32-mediated turnover of a maternal mRNA activator in C.elegans. Scientists progress (2022). two: 10.1126/sciadv.abn0897

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