Marcos Simões-Costa asks how cells in the embryo get their identities

Growing up in Brazil, Marcos Simões-Costa often visited his grandparents’ farm in the Amazon. That immersion in nature — squawking toucans and all — sparked his fascination with science and evolution. But a video of a developing embryo, shown in his middle school science class, cemented his desire to become a developmental biologist.

“It’s such a beautiful process,” he says. “I was always into drawing and art, and it was very visual — the shapes of the embryo changing, the fact that you start with one cell and the complexity is increasing. I just got lost in that video.”

Today, Simões-Costa, of Harvard Medical School and Boston Children’s Hospital, is honoring his younger self by demystifying how the embryo develops. He studies the embryos and stem cells of birds and mice to learn how networks of genes and the elements that control them influence the identity of cells. The work could lead to new treatments for various diseases, including cancer.

“The embryo is our best teacher,” he says.
Standout research
Simões-Costa focuses on the embryo’s neural crest cells, a population of stem cells that form in the developing central nervous system. The cells migrate to other parts of the embryo and give rise to many different cell types, from the bone cells of the face to muscle cells to brain and nerve cells.

Scientists have wondered for years why, despite being so similar, neural crest cells in the cranial region of the embryo can form bone and cartilage, while those in the trunk region can’t form either. While a postdoc at Caltech, Simões-Costa studied the cascade of molecules that govern how genes are expressed in each cell type. With his adviser, developmental biologist Marianne Bronner, he identified transcription factors — proteins that can turn genes on and off — that were present only in cranial cells. Transplanting the genes for those proteins into trunk cells endowed the cells with the ability to create cartilage and bone.

Now in his own lab, he continues to piece together just how this vast regulatory network influences the specialization of cells. His team reconstructed how neural crest cells’ full set of genetic instructions, or the genome, folds into a compact, 3-D shape. The researchers identified short DNA sequences, called enhancers, that are located in faraway regions of the genome, but end up close to key genes when the genome folds. These enhancers work with transcription factors and other regulatory elements to control gene activity.

Simões-Costa is also using neural crest cells to elucidate a strange behavior shared by cancer cells and some embryonic cells. These cells produce energy anaerobically, without oxygen, even when oxygen is present. Called the Warburg effect, this metabolic process has been studied extensively in cancer cells, but its function remained unclear.

Colored tracks representing cell movements..
Through experiments manipulating the metabolism of neural crest cells, Simões-Costa’s team found that the Warburg effect is necessary for the cells to move around during early development. The mechanism, which should stay turned off in nonembryonic cells, somehow “gets reactivated in adult cells in the context of cancer, leading those cells to become more migratory and more invasive,” Simões-Costa says.

“He’s one of the few people who’s really looked at [this process in neural crest cells] at a molecular level and done a deep dive into the mechanisms underlying it,” says Bronner.

Cleverly combining classical embryological methods with the latest genomic technologies to address fundamental questions in developmental biology is what makes Simões-Costa special, says Kelly Liu, a developmental biologist at Cornell University. He wants to understand not only what individual genes do, but how they work at a systems level, she says.

What’s next
How does the genetic blueprint tell cells where they are in the embryo, and what they should be doing? How do cancer cells hijack the Warburg effect, and could understanding of that process lead to new treatments? These are some of the questions Simões-Costa wants to tackle next.

“It’s been 20 years since the Human Genome Project came to a conclusion,” he says, referring to the massive effort to read the human genetic instruction book. “But there’s still so much mystery in the genetic code.”

Those mysteries, plus a deep passion for lab work, fuel Simões-Costa’s research. “Being at the bench is when I’m the happiest,” he says. He likens the delicate craft of performing precise surgeries on tissues and cells to meditation. “It does not get old.”

Mangrove forests expand and contract with a lunar cycle

The glossy leaves and branching roots of mangroves are downright eye-catching, and now a study finds that the moon plays a special role in the vigor of these trees.

Long-term tidal cycles set in motion by the moon drive, in large part, the expansion and contraction of mangrove forests in Australia, researchers report in the Sept. 16 Science Advances. This discovery is key to predicting when stands of mangroves, which are good at sequestering carbon and could help fight climate change, are most likely to proliferate (SN: 11/18/21). Such knowledge could inform efforts to protect and restore the forests.
Mangroves are coastal trees that provide habitat for fish and buffer against erosion (SN: 9/14/22). But in some places, the forests face a range of threats, including coastal development, pollution and land clearing for agriculture. To get a bird’s-eye view of these forests, Neil Saintilan, an environmental scientist at Macquarie University in Sydney, and his colleagues turned to satellite imagery. Using NASA and U.S. Geological Survey Landsat data from 1987 to 2020, the researchers calculated how the size and density of mangrove forests across Australia changed over time.

After accounting for persistent increases in these trees’ growth — probably due to rising carbon dioxide levels, higher sea levels and increasing air temperatures — Saintilan and his colleagues noticed a curious pattern. Mangrove forests tended to expand and contract in both extent and canopy cover in a predictable manner. “I saw this 18-year oscillation,” Saintilan says.

That regularity got the researchers thinking about the moon. Earth’s nearest celestial neighbor has long been known to help drive the tides, which deliver water and necessary nutrients to mangroves. A rhythm called the lunar nodal cycle could explain the mangroves’ growth pattern, the team hypothesized.

Over the course of 18.6 years, the plane of the moon’s orbit around Earth slowly tips. When the moon’s orbit is the least tilted relative to our planet’s equator, semidiurnal tides — which consist of two high and two low tides each day — tend to have a larger range. That means that in areas that experience semidiurnal tides, higher high tides and lower low tides are generally more likely. The effect is caused by the angle at which the moon tugs gravitationally on the Earth.

Saintilan and his colleagues found that mangrove forests experiencing semidiurnal tides tended to be larger and denser precisely when higher high tides were expected based on the moon’s orbit. The effect even seemed to outweigh other climatic drivers of mangrove growth, such as El Niño conditions. Other regions with mangroves, such as Vietnam and Indonesia, probably experience the same long-term trends, the team suggests.

Having access to data stretching back decades was key to this discovery, Saintilan says. “We’ve never really picked up before some of these longer-term drivers of vegetation dynamics.”

It’s important to recognize this effect on mangrove populations, says Octavio Aburto-Oropeza, a marine ecologist at the Scripps Institution of Oceanography in La Jolla, Calif., who was not involved in the research.

Scientists now know when some mangroves are particularly likely to flourish and should make an extra effort at those times to promote the growth of these carbon-sequestering trees, Aburto-Oropeza says. That might look like added limitations on human activity nearby that could harm the forests, he says. “We should be more proactive.”

Here’s how olivine may trigger deep earthquakes

Cocooned within the bowels of the Earth, one mineral’s metamorphosis into another may trigger some of the deepest earthquakes ever detected.

These cryptic tremors — known as deep-focus earthquakes — are a seismic conundrum. They violently rupture at depths greater than 300 kilometers, where intense temperatures and pressures are thought to force rocks to flow smoothly. Now, experiments suggest that those same hellish conditions might also sometimes transform olivine — the primary mineral in Earth’s mantle — into the mineral wadsleyite. This mineral switch-up can destabilize the surrounding rock, enabling earthquakes at otherwise impossible depths, mineral physicist Tomohiro Ohuchi and colleagues report September 15 in Nature Communications.
“It’s been a real puzzle for many scientists because earthquakes shouldn’t occur deeper than 300 kilometers,” says Ohuchi, of Ehime University in Matsuyama, Japan.

Deep-focus earthquakes usually occur at subduction zones where tectonic plates made of oceanic crust — rich in olivine — plunge toward the mantle (SN: 1/13/21). Since the quakes’ seismic waves lose strength during their long ascent to the surface, they aren’t typically dangerous. But that doesn’t mean the quakes aren’t sometimes powerful. In 2013, a magnitude 8.3 deep-focus quake struck around 609 kilometers below the Sea of Okhotsk, just off Russia’s eastern coast.

Past studies hinted that unstable olivine crystals could spawn deep quakes. But those studies tested other minerals that were similar in composition to olivine but deform at lower pressures, Ohuchi says, or the experiments didn’t strain samples enough to form faults.

He and his team decided to put olivine itself to the test. To replicate conditions deep underground, the researchers heated and squeezed olivine crystals up to nearly 1100° Celsius and 17 gigapascals. Then the team used a mechanical press to further compress the olivine slowly and monitored the deformation.

From 11 to 17 gigapascals and about 800° to 900° C, the olivine recrystallized into thin layers containing new wadsleyite and smaller olivine grains. The researchers also found tiny faults and recorded bursts of sound waves — indicative of miniature earthquakes. Along subducting tectonic plates, many of these thin layers grow and link to form weak regions in the rock, upon which faults and earthquakes can initiate, the researchers suggest.

“The transformation really wreaks havoc with the [rock’s] mechanical stability,” says geophysicist Pamela Burnley of the University of Nevada, Las Vegas, who was not involved in the research. The findings help confirm that olivine transformations are enabling deep-focus earthquakes, she says.

Next, Ohuchi’s team plans to experiment on olivine at even higher pressures to gain insights into the mineral’s deformation at greater depths.