In June, 100 Drosophila scientists gathered on the Greek island of Crete for their biennial conference. Among them was Cassandra Extavour, a Canadian geneticist at Harvard University. Her lab uses fruit flies to study evolution and development. It is “evo devo”. Most often, such scientists choose the species Drosophila melanogaster as the ‘model organism’. Nobel Prize in physiology and medicine.
However, Dr. Extavour is also known for breeding alternative species as model organisms. She is especially keen on crickets, especially her Gryllus bimaculatus. This is despite her not yet enjoying the fruit fly’s following. (About 250 principal investigators had applied to attend the meeting in Crete.)
During a video interview from her hotel room, she said while slapping the beetle, “That’s crazy.” There is a possibility.”
cricket I have already participated in research on circadian clocks, limb regeneration, learning and memory. They have served as disease models and pharmaceutical factories. A true polymath, cricket! is also gaining popularity. food, chocolate covered or not. From an evolutionary perspective, crickets have an increasing opportunity to learn about the last common ancestor of insects. It has more characteristics in common with other insects than fruit flies. (Notably, insects make up more than 85% of his animal species).
Dr. Extavour’s research aims at the basics of how the embryo works. And what does that reveal about how the first animals were born? All animal embryos follow a similar journey. Single cells become numerous and are arranged in the superficial layers of the egg, providing the initial blueprint for all parts of the adult body. But how do embryonic cells—cells that have the same genome but don’t all do the same thing with that information—know where to go and what to do? ?
“It’s a mystery to me,” Dr. Extaver said. “It’s always where I want to go.”
Seth Donoughe, a biologist and data scientist at the University of Chicago and an alumnus of Dr. Extavour’s lab, describes embryology as how a developing animal “puts the right part at the right place at the right time.” I explained that it was a study of how to make it. Some new research featuring amazing videos of a cricket embryo show that certain “right parts” (cell nuclei) are moving in his three dimensions. geometry I am playing the lead role.
Humans, frogs, and many other animals that have been extensively studied begin as single cells that quickly divide again and again into separate cells. In crickets and most other insects, initially only the cell nucleus divides, forming many nuclei that move throughout the shared cytoplasm and later form their own cell membrane.
In 2019, Stefano Di Talia, a quantitative developmental biologist at Duke University, said: studied the movement of the Drosophila nucleus and showed that they are transported by pulsating currents in the cytoplasm. It’s a bit like a leaf moving over a slow-moving eddy current.
But a different mechanism was at work in cricket embryos. Researchers watched and analyzed the microscopic dance of the nucleus for hours. The glowing nubs split and move in cryptic patterns, but they are neither perfectly orderly nor completely random, but with different directions and velocities, with adjacent nuclei more synchronized than distant ones. increase. The performance did not believe in choreography beyond mere physics and chemistry.
“The shapes that nuclei adopt are the result of their ability to sense and react to the density of other nuclei in their vicinity,” says Dr. Extavour. Dr. Di Talia was not involved in the new research, but he was inspiring. “This is a great study of a beautiful system that is very biologically relevant,” he said.
nuclear journey
Cricket researchers initially took a classical approach. “We just saw it,” Dr. Extaver said.
They captured the video using a laser light sheet microscope. Snapshots captured a nuclear dance every 90 seconds during his first eight hours of embryonic development. (Crickets hatch in about two weeks.)
Biological materials are usually translucent and difficult to see even with the most sophisticated microscopes. But Taro Nakamura, then a postdoc in Dr. Extavour’s lab and now a developmental biologist at the National Institute for Basic Biology in Okazaki, Japan, said: A special strain of cricket at its core glowing fluorescent greenAs Dr. Nakamura said, when he documented embryo development, the results were “amazing.”
That was the “starting point” of the exploratory process, Dr. Donoughe said. He paraphrased a remark that is sometimes attributed to Asimov, the author of his fictional science and professor of biochemistry, Isaac. When they discover something, they say, ‘Huh. That’s weird.'”
Initially, biologists watched a video on a loop on a conference room screen. This is the equivalent of an IMAX cricket, given that the embryo is about one-third the size of a (long grain) rice grain. They tried to detect patterns, but the dataset was overwhelming. They needed more quantitative knowledge.
Dr. Donoughe contacted Christopher Rycroft, now an applied mathematician at the University of Wisconsin-Madison, and showed him the dancing nuclei. ‘Wow! ‘ said Dr. Rycroft. Although he had never seen anything like it, he recognized the potential for data-driven collaboration. He and Jordan Hoffman, then a doctoral student in Dr. Rycroft’s lab, participated in the study.
Over several rounds of screening, the math and biology team pondered many questions: How many nuclei were there? When did they start dividing? what direction were they going? where did they end up? Why were some twirling and others crawling?
Dr. Rycroft often stands at the crossroads of the life sciences and the physical sciences. (Last year he published on the physics of paper crumpling.) Dr. Extavour says the same thing.
The team spent a lot of time chasing ideas on the whiteboard, often drawing. This problem reminded Dr. Rycroft of the Voronoi diagram. geometric structure Divide the space into non-overlapping subregions (polygons, or Voronoi cells, each diverging from a seed point). It’s a versatile concept that can be applied to many things, including clusters of galaxies, wireless networks, and canopy growth patterns. (The tree trunk is the seed point and the crown is the Voronoi cells, which nestle closely but do not encroach on each other. This phenomenon is known as crown embarrassment.)
In the context of cricket, the researchers calculated the Voronoi cells surrounding each nucleus and observed that the shape of the cell helped predict the direction in which the nucleus would move next. Basically, Dr. Donneau said, “the nuclei tended to migrate into nearby open space.”
Geometry, he pointed out, provides an abstracted way of thinking about cell dynamics. “For most of the history of cell biology, we have not been able to directly measure or observe mechanical forces,” he said. However, researchers were able to observe higher-order geometric patterns generated by the dynamics of these cells. “So when you think about cell spacing, cell size, and cell shape, we know that they arise from mechanical constraints on a very fine scale,” Dr. Donoughe said.
To extract this kind of geometric information from cricket videos, Dr. Donau and Dr. Hoffmann tracked the nucleus step by step and measured its position, velocity and orientation.
“This is not a trivial process and ultimately involves many forms of computer vision and machine learning,” says Dr. Hoffmann, an applied mathematician now at DeepMind in London. .
We also manually validated the software results and clicked on 100,000 positions to connect nuclear lineages through space and time. Dr. Hoffman found it boring. Dr. Donoughe thought of it like playing a video game.
We then developed a computational model to test and compare possible hypotheses to explain the motion and position of nuclei. Overall, they ruled out the cytoplasmic flow that Dr. Di Talia saw in fruit flies. They disproved random motion and the idea that atomic nuclei were physically pushing against each other.
Instead, they arrived at a plausible explanation based on another known mechanism in Drosophila and roundworm embryos. Small molecular motors in the cytoplasm, with clusters of microtubules extending from each nucleus, unlike the forest canopy.
The team proposed that a similar type of molecular force pulls the cricket’s nucleus into the vacant space. “The molecule could be a microtubule, but we don’t know for sure,” Dr. Extavour said in an email. “We need to do more experiments in the future to find out.”
Geometry of Diversity
This cricket odyssey would not be complete without mentioning the custom ’embryo retractor’ that Dr. Donoughe created to test various hypotheses.it replicated old school The technology was motivated by previous work on evolution with Dr. Extavour and others. egg size and shape.
This contraption allowed Dr. Donow to perform the tedious task of looping human hair around a cricket egg. This formed two regions of him containing the original nucleus and two regions of him in the partially cut out annex.
After that, the researchers again looked at nuclear choreography. In the original region, the velocity decreased when the nuclei reached dense densities. But a few nuclei slipped through the constriction tunnels, picked up speed again, and let loose like horses in the open pastures.
This is the strongest evidence that nuclear motion was governed by geometry, and “may plausibly coordinate global chemical signals, currents, or whole-embryonic behavior.” It is not controlled by almost all hypotheses of ,” said Dr.
By the end of the study, the team had amassed over 40 terabytes of data on 10 hard drives and improved computational geometric models that would be added to Cricket’s toolkit.
Dr. Extavour said:
The model can simulate any egg size and shape, making it useful as a “test ground for other insect embryos,” Dr. Extavour said. She said this would allow us to compare diverse species and explore their evolutionary histories in greater depth.
But the greatest reward of this study, agreed by all researchers, was the spirit of cooperation.
“There is a place and time for expertise,” said Dr. Extavour. “In scientific discovery, we need to expose ourselves to people who are less invested in a particular outcome than we are.”
The questions posed by mathematicians were “free from prejudices of any kind,” says Dr. Extavour. “These are the most exciting questions.”
