By Kurtis Chien
Mice have traditionally been used as research models for the study of human embryonic development, since they share many early developmental processes, and researchers have the most comprehensive map of their genome. However, recent use of CRISPR-Cas9, a gene editing tool, has allowed for more thorough investigation into the early development of other, similar animals. Bovines, in particular, have been determined to exhibit even closer processes to humans.
Mammalian embryos begin dividing after fertilization. Following a couple of divisions, the cells form a blastocyst, which is two layers of cells wrapped around a cavity filled with fluid. The inner layer of cells become the actual embryo, and the outer layer becomes extraembryonic membranes and the placenta. Some of the cells on the inner layer of the blastocyst are pluripotent stem cells, and are capable of developing into a variety of different adult cells.
Here’s where the difference with mice begins. Researchers at the Ludwig-Maximilians-Universitaet in Munich were able to use CRISPR-Cas9 to delete OCT4, a gene that regulates the pluripotency of embryonic stem cells. When OCT4 was deleted from a mouse embryo, the researchers observed that the embryo was unable to express a transcription factor called GATA6, which contributes to heart, lung, and gut development. Deletion of OCT4 from a bovine embryo, on the other hand, resulted in the loss of the transcription factor NANOG instead. This omission of NANOG is also observed in human embryos with mutated or dysfunctional OCT4.
OCT4 deletion is just one example of a handful that support the developmental similarities between human and bovine embryos. These findings, and the future use of bovine models, might give rise to a better understanding of how human embryos develop, and what each step of the process means.
Kilian Simmet, Valeri Zakhartchenko, Julia Philippou-Massier, Helmut Blum, Nikolai Klymiuk, Eckhard Wolf. OCT4/POU5F1 is required for NANOG expression in bovine blastocysts. Proceedings of the National Academy of Sciences, 2018; 201718833 DOI: 10.1073/pnas.1718833115
“GATA6 Gene.” GeneCards, Weizmann Institute of Science, www.genecards.org/cgi-bin/carddisp.pl?gene=GATA6.