Magic embryology: tight cell junctions control events (Introduction)

by David Turell , Tuesday, July 18, 2023, 14:16 (495 days ago) @ David Turell

Growing embryos in the lab:

https://phys.org/news/2023-07-key-function-tight-junctions-embryo.html

"As a human embryo grows, a set of molecules directs cells as they multiply and take on specific identities and spatial positions within the embryo. In one crucial step known as gastrulation, these signaling molecules guide a single layer of embryonic stem cells to form three layers of distinct cell types that will later become different parts of the body.

"Now, researchers in the iPS Cell Research Center at Gladstone Institutes have shown that tight junctions between cells may play a critical role in gastrulation in human embryos.

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"Gastrulation sets a foundation for the development of the entire human body. Researchers have found ways to recreate a simplified version of this fundamental process in a dish by starting with a layer of induced pluripotent stem cells, or iPS cells—adult cells that have been reprogrammed to mimic embryonic stem cells, meaning they can differentiate to become any cell type in the body.

"Then, scientists add a protein called BMP4, a key signaling molecule in gastrulation, which causes the cells in the dish to begin to form the three layers of cells found in the embryo. However, since all of the cells appear to receive the same BMP4 signal, it has been unclear why some transform into one cell type while others become different cell types.

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"Yamanaka, Vasic, and their team found that growing the cells in a less-confined space allowed the tight junctions to assemble consistently. When they added BMP4 to the unconfined cells, they got their "aha" moment: only cells at the edge of the cluster received enough BMP4 to activate molecular pathways that would nudge them to become different layer cell types.

"'Tight junctions between adjacent cells seem to make them impervious to signals from BMP4," Vasic says. "But the edge cells don't have a buddy to form tight junctions with on their outer side, which means they are getting the strongest cues from BMP4."

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"'We showed that removing the tight junctions made all the cells respond to BMP4," says Yamanaka, who is also a professor of anatomy at UC San Francisco, as well as director emeritus and professor at the Center for iPS Cell Research and Application (CiRA), Kyoto University, in Japan. "This suggests that tight junctions block cells from responding to signals in gastrulation models, and more fundamentally, that the structure of cells is very important to how they receive differentiation signals."

"'Broadly speaking, this study demonstrates how perturbations to innate properties of iPS cells can modulate their sensitivity to extracellular cues and alter their cell fate trajectory," says Todd McDevitt, Ph.D., former senior investigator at Gladstone and a senior author of the study. "This principle could be a game changer for unlocking the potential of iPS cells to produce more homogeneous populations of differentiated cells for therapeutic applications.'"

Comment: these studies with cells are the only way we can interpret how the embryo is controlled in development. The appearance of a designed process is obvious.