Egg cells are by far the most important cells produced by most organisms. In people, they’re a number of occasions bigger than a typical physique cell and about 10,000 occasions bigger than sperm cells.
There is a cause why egg cells, or oocytes, are so large: They should accumulate sufficient vitamins to assist a rising embryo after fertilization, plus mitochondria to energy all of that development. Nevertheless, biologists do not but perceive the complete image of how egg cells turn into so giant.
A brand new examine in fruit flies, by a group of MIT biologists and mathematicians, reveals that the method via which the oocyte grows considerably and quickly earlier than fertilization depends on bodily phenomena analogous to the alternate of gases between balloons of various sizes. Particularly, the researchers confirmed that “nurse cells” surrounding the a lot bigger oocyte dump their contents into the bigger cell, simply as air flows from a smaller balloon into a bigger one when they’re linked by small tubes in an experimental setup.
“The examine exhibits how physics and biology come collectively, and the way nature can use bodily processes to create this sturdy mechanism,” says Jörn Dunkel, an MIT affiliate professor of bodily utilized arithmetic. “If you wish to develop as an embryo, one of many objectives is to make issues very reproducible, and physics offers a really sturdy approach of reaching sure transport processes.”
Dunkel and Adam Martin, an MIT affiliate professor of biology, are the senior authors of the paper, which seems this week within the Proceedings of the Nationwide Academy of Sciences. The examine’s lead authors are postdoc Jasmin Imran Alsous and graduate scholar Nicolas Romeo. Jonathan Jackson, a Harvard College graduate scholar, and Frank Mason, a analysis assistant professor at Vanderbilt College Faculty of Medication, are additionally authors of the paper.
A bodily course of
In feminine fruit flies, eggs develop inside cell clusters often known as cysts. An immature oocyte undergoes 4 cycles of cell division to supply one egg cell and 15 nurse cells. Nevertheless, the cell separation is incomplete, and every cell stays linked to the others by slender channels that act as valves that enable materials to move between cells.
Members of Martin’s lab started learning this course of due to their longstanding curiosity in myosin, a category of proteins that may act as motors and assist muscle cells contract. Imran Alsous carried out high-resolution, dwell imaging of egg formation in fruit flies and located that myosin does certainly play a task, however solely within the second part of the transport course of. Through the earliest part, the researchers had been puzzled to see that the cells didn’t seem like rising their contractility in any respect, suggesting that a mechanism apart from “squeezing” was initiating the transport.
“The 2 phases are strikingly apparent,” Martin says. “After we noticed this, we had been mystified, as a result of there’s actually not a change in myosin related to the onset of this course of, which is what we had been anticipating to see.”
Martin and his lab then joined forces with Dunkel, who research the physics of soppy surfaces and flowing matter. Dunkel and Romeo puzzled if the cells may be behaving the identical approach that balloons of various sizes behave when they’re linked. Whereas one would possibly count on that the bigger balloon would leak air to the smaller till they’re the identical dimension, what truly occurs is that air flows from the smaller to the bigger.
This occurs as a result of the smaller balloon, which has better curvature, experiences extra floor pressure, and due to this fact increased strain, than the bigger balloon. Air is due to this fact pressured out of the smaller balloon and into the bigger one. “It is counterintuitive, nevertheless it’s a really sturdy course of,” Dunkel says.
Adapting mathematical equations that had already been derived to clarify this “two-balloon impact,” the researchers got here up with a mannequin that describes how cell contents are transferred from the 15 small nurse cells to the massive oocyte, primarily based on their sizes and their connections to one another. The nurse cells within the layer closest to the oocyte switch their contents first, adopted by the cells in additional distant layers.
“After I spent a while constructing a extra sophisticated mannequin to clarify the 16-cell downside, we realized that the simulation of the less complicated 16-balloon system appeared very very similar to the 16-cell community. It’s stunning to see that such counterintuitive however mathematically easy concepts describe the method so effectively,” Romeo says.
The primary part of nurse cell dumping seems to coincide with when the channels connecting the cells turn into giant sufficient for cytoplasm to maneuver via them. As soon as the nurse cells shrink to about 25 p.c of their unique dimension, leaving them solely barely bigger than their nuclei, the second part of the method is triggered and myosin contractions power the remaining contents of the nurse cells into the egg cell.
“Within the first a part of the method, there’s little or no squeezing happening, and the cells simply shrink uniformly. Then this second course of kicks in towards the top the place you begin to get extra energetic squeezing, or peristalsis-like deformations of the cell, that full the dumping course of,” Martin says.
The findings exhibit how cells can coordinate their habits, utilizing each organic and bodily mechanisms, to result in tissue-level habits, Imran Alsous says.
“Right here, you will have a number of nurse cells whose job it’s to nurse the longer term egg cell, and to take action, these cells seem to move their contents in a coordinated and directional method to the oocyte,” she says.
Oocyte and early embryonic improvement in fruit flies and different invertebrates bears some similarities to these of mammals, nevertheless it’s unknown if the identical mechanism of egg cell development may be seen in people or different mammals, the researchers say.
“There’s proof in mice that the oocyte develops as a cyst with different interconnected cells, and that there’s some transport between them, however we do not know if the mechanisms that we’re seeing right here function in mammals,” Martin says.
The researchers are actually learning what triggers the second, myosin-powered part of the dumping course of to begin. They’re additionally investigating how adjustments to the unique sizes of the nurse cells would possibly have an effect on egg formation.
The analysis was funded by the Nationwide Institute of Normal Medical Sciences, a Complicated Programs Scholar Award from the James S. McDonnell Basis, and the Robert E. Collins Distinguished Scholarship Fund.