Magic embryology: it is all in the timing (Introduction)

by David Turell @, Friday, October 19, 2018, 20:51 (666 days ago) @ Balance_Maintained

Making a fetus involves the timing of DNA expression and particular protein productions all in 3-D. This is an interview with a scientist studying how embryology works:

Q: But developmental timing is important not just for the immediate survival of the embryo, but for health and disease further down the line, right?

"Yes, that’s one of our big hypotheses, because of the role timing plays in deciding the fates of cells. The idea is that development starts with a certain timeline. If a cell does not make it to a certain stage on time, its cell fate can change, and it’s typically thrown out of the tissue. It’s expelled and it dies.

"In a paper in Nature Genetics in 2016, for instance, we identified nearly 150 new genes, many of which were retroviral, that get expressed very early on in human stem cells. Then, when we turned some of the retroviral genes off, we found it changed the fate of the cells. Instead of becoming embryonic stem cells — which ultimately give rise to the fetus — the cells could only contribute to the trophectoderm layer, which gives rise to the tissues that attach the embryo to the uterus. The trophectoderm is made up in part of “bad” cells that won’t make it as part of the fetus.

"Which means that part of the puzzle on timing and which cells become part of the embryo and which become part of the extra-embryonic tissue depends on human-specific sequences that we inherited from retroviral integration.

Q: That seems surprising — that viral DNA would play such an important role so early in development.

Over the course of evolution, viruses have been in us and on us and changing us continually. We wrote another paper in Nature with Joanna Wysocka at Stanford, suggesting that these viral sequences have another, second effect: that they not only contribute to cell fate but also help the embryo get rid of viral infections.

In both cases, then, it seems like we have a cleanup system early in development that’s viral-based.

Q: You also study factors that determine whether or not cells will become germ cells. What’s at play there?

"In a paper published in Nature Cell Biology in April, we identified a triad of proteins that interact to help form primordial germ cells and maintain the primordial germ cell fate.

"We knew that the protein OCT4 is one of the master regulators of embryonic development and cell fate. But how do you tell if an embryonic cell will form a primordial germ cell, given that both express OCT4? We thought OCT4 could be acting with different partners in specific ways to enable the birth of the germ line.
That’s what a decision looks like in cells. You can think of it as a fulcrum: The stem cell sits in the middle, and if OCT4 and the other proteins are acting in concert, that fulcrum will tilt toward the germ line. If one of the proteins isn’t present in the right amount, we found that the cells instead become ectoderm, embryonic tissue that typically gives rise to neurons. It’s a delicate balance. We’re now starting to unpack each protein’s actual function in embryonic and germ cell development, and we’re studying how other transcription factors might be involved."

Comment: Darwin could not comment about embryology, as the science didn't exist. But the intricacies of embryology in timing of various tissues in production and requirement in 3-D for proper placement of the geography of a whole organism is still mostly a mystery. An embryo is not like a new auto on a production line, where one section is added at a time. In embryology the whole organism is having all different parts all at the same time, once the basic stem cells are organized in position. All of this requires design. Chance attempts won't work.

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