Magic embryology: jumpstarting embryogenesis (Introduction)

by David Turell , Monday, July 24, 2023, 01:12 (279 days ago) @ David Turell

After egg and sperm join:

https://www.sciencedaily.com/releases/2023/07/230721113116.htm

"It has been known for some time that the genome of a newly fertilized egg cell is inactive and has to be woken up, said Richard Schultz, research professor at the University of California, Davis, School of Veterinary Medicine and a corresponding author on the paper. This step is called zygote genome activation.

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"For the resetting or awakening process to occur, the embryo needs to start transcribing genes from its DNA into messenger RNA that are in turn translated into proteins. The first genes transcribed will activate other genes, implementing the program that will allow the embryo to develop into a complete mouse (or human). The identity of those first master-regulator genes has been unknown until now.

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"RNA polymerase II (Pol II) is the enzyme that transcribes DNA to RNA. But Pol II by itself is a dumb enzyme, Schultz said. Other genes, called transcription factors, are needed to instruct Pol II so that it transcribes the "correct" genes at the right time.

"In the early 2000s, Schultz had the insight that those first transcription factors would be found among dormant maternal messenger RNAs in the egg cell. Dormant maternal messenger RNAs are unique to oocytes because the newly synthesized messenger RNA is not translated as it is in somatic cells. As the oocyte matures to become an egg, these dormant maternal messenger RNAs are translated into proteins that then execute their function. Schultz realized that the information to start zygote genome activation would be in a dormant messenger RNA from the mother that would encode a master transcription factor.

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"Schultz's lab identified a large family of genes called OBOX as likely candidates. The family consists of 8 genes, OBOX1-8. Based on their expression profiles during early development, OBOX1, 2, 3, 4, 5, and 7 were likely candidates. They began working with Wei Xie at Tsinghua University, Beijing to narrow down the candidates.

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"Most interesting, and unanticipated, was that the function of these OBOX genes was highly redundant: a knockout of one could be replaced by another. That redundancy has likely evolved because the transition is so important, Schultz said. In addition, the researchers found that the OBOX genes function by facilitating Pol II locating to the correct genes to begin zygote genome activation.

"In mice, genome activation occurs at the two-cell stage. In human embryos, it occurs later, when the embryo has gone through a couple of rounds of division to form eight cells. An open question is how conserved this process is across species, i.e., are OBOX-like genes involved in genome activation in humans. The work also has implications for understanding how embryonic stem cells are reprogrammed so that they can develop into any tissue of the body."

Comment: the step to sexual reproduction undoubtedly facilitated evolution, but added huge complexity to the reproductive process of simple cell splitting. The early zygotic kick-start is a series of events that is irreducibly complex and must be designed all at once to be effective. Without this design the species will not reproduce.