But how do cells fold themselves so precisely into such complicated configurations during development? What are the fundamental forces driving this process?

Now, researchers at Harvard Medical School have discovered a mechanical process by which sheets of cells morph into the delicate, looping semicircular canals of the inner ear.

Published Dec. 22 in Cell, the research, done in zebrafish, reveals that the process involves a combination of hyaluronic acid, produced by cells, that swells with water, and thin connectors between cells that direct the force of this swelling to shape the tissue.

Although conducted in zebrafish, the work reveals a basic mechanism for how tissues take on shapes — one that is likely to be conserved across vertebrates, the researchers say, and may also have implications for bioengineering.

A Model of Transparency

Study senior author Sean Megason, professor of systems biology in the Blavatnik Institute at HMS, and his team study how cells develop into complex, three-dimensional structures. To address this question, they turned to a classic — and ideal — model organism: zebrafish.

“They’re transparent, so we just stick them under a microscope and look at this entire process from a single cell to a larva that can swim and has all its parts,” explained study first author Akankshi Munjal, who conducted the research as a postdoctoral researcher at HMS and is now an assistant professor of cell biology at Duke University.

These parts include the semicircular canals, three fluid-filled tubes in the inner ear that are needed for balance and orienting in space. Little is known about how the semicircular canals form, in part because in many species they are obscured by the middle and outer ear. In zebrafish, however, the canals sit close to the surface, allowing researchers to watch them develop under a microscope.

“This was an exciting opportunity for us to look at how a three-dimensional organ forms from a simple sheet of cells,” Munjal said. “We could look at the inner ear in the embryo with complete accessibility.”

“The inner ear is a model for how cells work together to make complex structures that are needed for organisms to function,” Megason added. “We went into it thinking it was a beautiful structure, but not knowing what we would find.”

What they did find surprised them.

The conventional thinking is that the proteins actin and myosin act as tiny motors inside cells, pushing and pulling them in different directions to fold a tissue into a specific shape. However, the researchers discovered that zebrafish semicircular canals form through a markedly different process. During development, the cells produce hyaluronic acid, which is perhaps most well known as an antiwrinkle agent in beauty products. Once in the extracellular matrix the acid swells up, not unlike a diaper in a swimming pool. This swelling creates enough force to physically move nearby cells, but since the pressure is the same in all directions, the researchers wondered how the tissue ends up stretching in one direction and not another to form an elongated shape. The team found that this is accomplished by thin connectors between cells — dubbed cytocinches — that constrain the force.

“It’s like if you were to put a corset on a water balloon and deform it into an oblong structure,” Munjal said. This combination of swelling and cinching progressively shapes an initially flat sheet of cells into tubes.

“Our work shows a new way of doing things,” Megason said, adding that he hopes it will encourage people to consider additional mechanisms that may be involved in shaping tissues. “Cells have to use many different forces in order to accomplish what they need to, and time will tell exactly what the balance is between the molecular approaches of actin and myosin and the more physical approaches of pressure.”

Their discovery likely has broader implications, Megason and Munjal added.

The genes that control hyaluronic acid production in zebrafish semicircular canals are also present in the semicircular canals of mammals, suggesting that a similar process may be occurring. Moreover, hyaluronic acid is found in multiple parts of the human body, including skin and joints, indicating that it may play a role in shaping many tissues and organs — an avenue for future research.

If that does turn out to be the case, then studying the genes involved in hyaluronic acid production could help researchers understand congenital defects in organs where hyaluronic acid drives development.

“This is likely to be a widespread, conserved mechanism across species and organs,” Munjal said.

The mechanism could also be applied to bioengineering, where researchers are attempting to prod stem cells into forming buds, tubes, and other complicated shapes, with the ultimate goal of culturing organs in the lab.

Lab-grown organs are still a work in progress, Megason noted, but a key step will be parsing how organs form inside an organism. “We’re trying to dissect the steps of how a complex organ such as the inner ear is made in vivo, and then quantitatively understand those steps,” Megason said. “We hope this will set the foundational groundwork for having cells grow into whatever pattern and shape we want.”

This work was supported by the National Institutes of Health (R01DC015478), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (K99HD098918), and a Human Frontier Science Program Long-Term Fellowship.

The researchers found an evolutionary tweak in feather nanostructure that has more than doubled the range of iridescent colors birds can display. This insight could help researchers understand how and when brilliant iridescence first evolved in birds, as well as inspire the engineering of new materials that can capture or manipulate light.

As iridescent birds move, nanoscale structures within their feathers’ tiny branch-like filaments — known as barbules — interact with light to amplify certain wavelengths depending on the viewing angle. This iridescence is known as structural coloration, wherein crystal-like nanostructures manipulate light.

“If you take a single barbule from an iridescent feather, cross-section it and put it under an electron microscope, you’ll see an ordered structure with black dots, or sometimes black rings or platelets, within a gray substrate,” said first author Klara Nordén, a Ph.D. student in the lab of senior author Mary Caswell Stoddard, associate professor of ecology and evolutionary biology at Princeton and associated faculty in Princeton’s High Meadows Environmental Institute (HMEI). “The black dots are pigment-filled sacs called melanosomes, and the gray surrounding them is feather keratin. I find these nanoscale structures just as beautiful as the colors they produce.”

Curiously, the melanosome structures come in variety of shapes. They can be rod-shaped or platelet-shaped, solid or hollow. Hummingbirds, for example, tend to have hollow, platelet-shaped melanosomes, while peacocks have rod-shaped melanosomes. But why birds evolved iridescent nanostructures with so many different types of melanosomes has been a mystery, with scientists unsure if some melanosome types are better than others at producing a broad range of vibrant colors.

To answer this question, the researchers combined evolutionary analysis, optical modeling and plumage measurements — all of which allowed them to uncover general design principles behind iridescent feather nanostructures.

Nordén and Stoddard worked with co-author Chad Eliason, a postdoctoral fellow at The Field Museum, to first survey the literature and compile a database of all described iridescent feather nanostructures in birds, which included more than 300 species. They then used a family tree of birds to illustrate which groups evolved the different melanosome types.

There are five primary types of melanosomes in iridescent feather nanostructures: thick rods, thin rods, hollow rods, platelets and hollow platelets. Except for thick rods, all of these melanosome types are found in brilliantly colored plumage. Because the ancestral melanosome type is rod-shaped, previous work focused on the two obvious features unique to iridescent structures: platelet shape and hollow interior.

However, when the researchers evaluated the results of their survey, they realized that there was a third melanosome feature that has been overlooked — thin melanin layers. All four melanosome types in iridescent feathers — thin rods, hollow rods, platelets and hollow platelets — create thin melanin layers, much thinner than a structure built with thick rods. This is important because the size of the layers in the structures is key to producing vibrant colors, Nordén said.

“Theory predicts that there is a kind of Goldilocks zone in which the melanin layers are just the right thickness to produce really intense colors in the bird-visible spectrum,” she said. “We suspected that thin rods, platelets or hollow forms may be alternative ways to reach that ideal thickness from the much larger ancestral melanosome size — the thick rods.”

The researchers tested their idea on bird specimens at the American Museum of Natural History in New York City by measuring the color of iridescent bird plumage that results from nanostructures with different melanosome types. They also used optical modeling to simulate the colors that would be possible to produce with different types of melanosomes. From these data, they determined which feature — thin melanin layers, platelet shape or hollowness — has the greatest influence on the range and intensity of color. Combining the results of the optical modeling and plumage analyses, the researchers determined that thin melanin layers — no matter the shape of the melanosomes — nearly doubled the range of colors an iridescent feather could produce.

“This key evolutionary breakthrough — that melanosomes could be arranged in thin melanin layers — unlocked new color-producing possibilities for birds,” Stoddard said. “The diverse melanosome types are like a flexible nanostructural toolkit, offering different routes to the same end: brilliant iridescent colors produced by thin melanin layers.”

This may explain why there exists such a great diversity of melanosome types in iridescent nanostructures. Iridescent nanostructures likely evolved many times in different groups of birds, but, by chance, thin melanin layers evolved from a thick rod in different ways. Some groups evolved thin melanin layers by flattening the melanosomes (producing platelets), others by hollowing out the interior of the melanosome (producing hollow forms), and yet others by shrinking the size of the rod (producing thin rods).

The findings of the study could be used to reconstruct brilliant iridescence in prehistoric animals, Nordén said. Melanosomes can be preserved in fossil feathers for millions of years, which means that paleontologists can infer original feather color — even iridescence — in birds and dinosaurs by measuring the size of fossilized melanosomes.

“Based on the thick solid rods that have been described in the plumage of Microraptor, for example, we can say that this feathered theropod likely had iridescent plumage much more like that of a starling than that of a peacock,” Nordén said.

The composition of melanosomes and keratin in bird feathers could hold clues for engineering advanced iridescent nanostructures that can efficiently capture or manipulate light, or be used to produce eco-friendly paints that do not require dyes or pigments. Super-black coatings such as Vantablack similarly use nanostructures that absorb and disperse rather than reflect light, similar to the black plumage of species in the birds-of-paradise (Paradisaeidae) family.

Iridescent feathers also could lead to a richer understanding of multifunctional materials, Nordén said. Unlike human-made materials, which are often developed for a single function, natural materials are inherently multipurpose. Melanin not only helps produce iridescence; it also protects birds from dangerous ultraviolet radiation, strengthens feathers and inhibits microbial growth.

“What if the different types of melanosomes initially evolved for some reason unrelated to the iridescent color — such as for making the feather mechanically stronger, or more resistant to microbial attack,” Nordén said. “These are some of the questions we are excited to tackle next.”

The embryo, dubbed ‘Baby Yingliang’, was discovered in the Late Cretaceous rocks of Ganzhou, southern China and belongs to a toothless theropod dinosaur, or oviraptorosaur. Among the most complete dinosaur embryos ever found, the fossil suggests that these dinosaurs developed bird-like postures close to hatching.

Scientists found the posture of ‘Baby Yingliang’ unique among known dinosaur embryos — its head lies below the body, with the feet on either side and the back curled along the blunt end of the egg. Previously unrecognised in dinosaurs, this posture is similar to that of modern bird embryos.

In modern birds, such postures are related to ‘tucking’ — a behaviour controlled by the central nervous system and critical for hatching success. After studying egg and embryo, researchers believe that such pre-hatching behaviour, previously considered unique to birds, may have originated among non-avian theropods.

Led by scientists from the University of Birmingham and China University of Geosciences (Beijing), the research team from institutions in China, UK and Canada today published its findings in iScience.

The embryo is articulated in its life position without much disruption from fossilisation. Estimated to be 27 cm long from head to tail, the creature lies inside a 17-cm-long elongatoolithid egg. The specimen is housed in Yingliang Stone Nature History Museum.

Fion Waisum Ma, joint first author and PhD researcher at the University of Birmingham, said: “Dinosaur embryos are some of the rarest fossils and most of them are incomplete with the bones dislocated. We are very excited about the discovery of ‘Baby Yingliang’ — it is preserved in a great condition and helps us answer a lot of questions about dinosaur growth and reproduction with it.

“It is interesting to see this dinosaur embryo and a chicken embryo pose in a similar way inside the egg, which possibly indicates similar prehatching behaviours.”

‘Baby Yingliang’ was identified as an oviraptorosaur based on its deep, toothless skull. Oviraptorosaurs are a group of feathered theropod dinosaurs, closely related to modern-day birds, known from the Cretaceous of Asia and North America. Their variable beak shapes and body sizes are likely to have allowed them to adopt a wide range of diets, including herbivory, omnivory and carnivory.

Birds are known to develop a series of tucking postures, in which they bend their body and bring their head under their wing, soon before hatching. Embryos that fail to attain such postures have a higher chance of death due to unsuccessful hatching.

By comparing ‘Baby Yingliang’ with the embryos of other theropods, long-necked sauropod dinosaurs and birds, the team proposed that tucking behaviour, which was considered unique to birds, first evolved in theropod dinosaurs many tens or hundreds of millions of years ago. Additional discoveries of embryo fossils would be invaluable to further test this hypothesis.

Professor Lida Xing from China University of Geosciences (Beijing), joint first author of the study, said: “This dinosaur embryo was acquired by the director of Yingliang Group, Mr Liang Liu, as suspected egg fossils around the 2000. During the construction of Yingliang Stone Nature History Museum in 2010s, museum staff sorted through the storage and discovered the specimens.

“These specimens were identified as dinosaur egg fossils. Fossil preparation was conducted and eventually unveiled the embryo hidden inside the egg. This is how ‘Baby Yingliang’ was brought to light.”

Professor Steve Brusatte from the University of Edinburgh, part of the research team, said: “This dinosaur embryo inside its egg is one of the most beautiful fossils I have ever seen. This little prenatal dinosaur looks just like a baby bird curled in its egg, which is yet more evidence that many features characteristic of today’s birds first evolved in their dinosaur ancestors.”

Because they lack an atmosphere, the moon and other airless bodies such as asteroids can build up an electric field through direct exposure to the sun and surrounding plasma. On the moon, this surface charge is strong enough to levitate dust more than 1 meter above the ground, much the way static electricity can cause a person’s hair to stand on end.

Engineers at NASA and elsewhere have recently proposed harnessing this natural surface charge to levitate a glider with wings made of Mylar, a material that naturally holds the same charge as surfaces on airless bodies. They reasoned that the similarly charged surfaces should repel each other, with a force that lofts the glider off the ground. But such a design would likely be limited to small asteroids, as larger planetary bodies would have a stronger, counteracting gravitational pull.

The MIT team’s levitating rover could potentially get around this size limitation. The concept, which resembles a retro-style, disc-shaped flying saucer, uses tiny ion beams to both charge up the vehicle and boost the surface’s natural charge. The overall effect is designed to generate a relatively large repulsive force between the vehicle and the ground, in a way that requires very little power. In an initial feasibility study, the researchers show that such an ion boost should be strong enough to levitate a small, 2-pound vehicle on the moon and large asteroids like Psyche.

“We think of using this like the Hayabusa missions that were launched by the Japanese space agency,” says lead author Oliver Jia-Richards, a graduate student in MIT’s Department of Aeronautics and Astronautics. “That spacecraft operated around a small asteroid and deployed small rovers to its surface. Similarly, we think a future mission could send out small hovering rovers to explore the surface of the moon and other asteroids.”

The team’s results appear in the current issue of the Journal of Spacecraft and Rockets. Jia-Richards’ co-authors are Paulo Lozano, the M. Alemán-Velasco Professor of Aeronautics and Astronautics and director of MIT’s Space Propulsion Lab; and former visiting student Sebastian Hampl, now at McGill University.

Ionic force

The team’s levitating design relies on the use of miniature ion thrusters, called ionic-liquid ion sources. These small, microfabricated nozzles are connected to a reservoir containing ionic liquid in the form of room-temperature molten salt. When a voltage is applied, the liquid’s ions are charged and emitted as a beam through the nozzles with a certain force.

Lozano’s team has pioneered the development of ionic thrusters and has used them mainly to propel and physically maneuver small satellites in space. Recently, Lozano had seen research showing the levitating effect of the moon’s charged surface on lunar dust. He also considered the electrostatic glider design by NASA and wondered: Could a rover fitted with ion thrusters produce enough repulsive, electrostatic force to hover on the moon and larger asteroids?

To test the idea, the team initially modeled a small, disk-shaped rover with ion thrusters that charged up the vehicle alone. They modeled the thrusters to beam negatively charged ions out from the vehicle, which effectively gave the vehicle a positive charge, similar to the moon’s positively charged surface. But they found this was not enough to get the vehicle off the ground.

“Then we thought, what if we transfer our own charge to the surface to supplement its natural charge?” Jia-Richards says.

By pointing additional thrusters at the ground and beaming out positive ions to amplify the surface’s charge, the team reasoned that the boost could produce a bigger force against the rover, enough to levitate it off the ground. They drew up a simple mathematical model for the scenario and found that, in principle, it could work.

Based on this simple model, the team predicted that a small rover, weighing about two pounds, could achieve levitation of about one centimeter off the ground, on a large asteroid such as Psyche, using a 10-kilovolt ion source. To get a similar liftoff on the moon, the same rover would need a 50-kilovolt source.

“This kind of ionic design uses very little power to generate a lot of voltage,” Lozano explains. “The power needed is so small, you could do this almost for free.”

In suspension

To be sure the model represented what could happen in a real environment in space, they ran a simple scenario in Lozano’s lab. The researchers manufactured a small hexagonal test vehicle weighing about 60 grams and measuring about the size of a person’s palm. They installed one ion thruster pointing up, and four pointing down, and then suspended the vehicle over an aluminum surface from two springs calibrated to counteract Earth’s gravitational force. The entire setup was placed within a vacuum chamber to simulate the airless environment of the moon and asteroids.

The researchers also suspended a tungsten rod from the experiment’s springs, and used its displacement to measure how much force the thrusters produced each time they were fired. They applied various voltages to the thrusters and measured the resulting forces, which they then used to calculate the height the vehicle alone could have levitated. They found these experimental results matched with predictions of the same scenario from their model, giving them confidence that its predictions for hovering a rover on Psyche and the moon were realistic.

The current model is designed to predict the conditions required to simply achieve levitation, which happened to be about 1 centimeter off the ground for a 2-pound vehicle. The ion thrusters could generate more force with larger voltage to lift a vehicle higher off the ground. But Jia-Richards says the model would need revising, as it doesn’t account for how the emitted ions would behave at higher altitudes.

“In principle, with better modeling, we could levitate to much higher heights,” he says.

In that case, Lozano says future missions to the moon and asteroids could deploy rovers that use ion thrusters to safely hover and maneuver over unknown, uneven terrain.

“With a levitating rover, you don’t have to worry about wheels or moving parts,” Lozano says. “An asteroid’s terrain could be totally uneven, and as long as you had a controlled mechanism to keep your rover floating, then you could go over very rough, unexplored terrain, without having to dodge the asteroid physically.”

This research was supported, in part, by NASA.