24 August

Cfap53 is important during the first cell divisions of an embryo

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Researchers from the group of Jeroen Bakkers discovered that the protein Cfap53 plays an important role in the very early development of the zebrafish embryo. This protein is present in both the egg cell and the sperm cell and is required for the first cell divisions of the developing embryo. Mutations in the gene that codes for Cfap53 have been found in children with severe birth defects, and the current study suggests that these children may have fertility problems in the future. The results from this study were published in the scientific journal Development on the 18th of August.

The fertilized egg starts dividing right after fertilization and over time forms a complete embryo. At first, the embryo does not produce its own proteins, but depends on proteins contributed by the egg cell (maternal factors) and the sperm cell (paternal factors). Most of the proteins that are known to be important for early development are contributed by the egg cell. The researchers used zebrafish to study the Cfap53 protein, and discovered that this protein is not only contributed to the embryo by the egg cell, but also by the sperm cell. When either the egg cell or the sperm cell lacks Cfap53, many of the zebrafish embryos do not develop.

Sven Willekers, first author of the study says about these embryos: “We were surprised that the egg cells were fertilized and that the DNA of the fertilized egg is still replicated in preparation of the first cell division, while further progression of the cell division does not occur.” As entire networks of proteins are involved in the first (and subsequent) cell divisions, the researchers set out to study the role of Cfap53 in this process. They found that Cfap53 plays a specific role in the formation of the mitotic spindle during the first cell divisions. The mitotic spindle is a structure that ensures the proper segregation of DNA to the two daughter cells. This explains why DNA replication does occur in embryos lacking Cfap53, but cell division itself does not.

Mutations in Cfap53 were initially identified in children with severe birth defects. In these children, the heart is not correctly formed and positioned in the body during development. The current study suggests that their clinical picture may extend to reduced fertility.

Publication
The centriolar satellite protein Cfap53 facilitates formation of the zygotic microtubule organizing center in the zebrafish embryo. Sven Willekers, Federico Tessadori, Babet van der Vaart, Heiko H. Henning, Riccardo Stucchi, Maarten Altelaar, Bernard A. J. Roelen, Anna Akhmanova and Jeroen Bakkers. Development 2022.

Portrait picture of Jeroen Bakkers

 

 

Jeroen Bakkers is group leader at the Hubrecht Institute and professor of Molecular Cardiogenetics at the UMC Utrecht.