Finding your way through the winding streets of certain cities can be a real challenge without a map. To orient ourselves, we rely on a variety of information, including digital maps on our phones, as well as recognizable shops and landmarks. Cells in our bodies face a similar problem when building our organs during embryogenesis. They need instructions on where to go and how to behave. Luckily, like cell phone towers in a city, embryos feature special cells in specific locations, known as organizers, that send signals to other cells and help them organize to build our complex organs.
Some of these signals are molecules sent from the organizer, a privileged signaling center. Cells around it receive stronger or weaker signals depending on their location, and they take decisions accordingly. Errors in the location of these messaging centers in the tissue lead to embryonic malformations that can be fatal. Scientists have known the relevance of these signaling centers for a long time, but how these appear at specific locations remained elusive.
Discovery Through International Collaboration
It took an international collaboration of physicists and biologists to pinpoint the answer. Several years ago, the laboratories of Prof. Ophir Klein at Cedars-Sinai Guerin Children’s and the University of California, San Francisco (UCSF), and Prof. Otger Campàs at the Physics of Life Excellence Cluster of TU Dresden and the University of California, Santa Barbara (UCSB), had a hint of how it may work and joined forces. Together, they figured out that it is the mechanical pressure inside the growing tissue that dictates where the signaling center will emerge.
“Our work shows that both mechanical pressure and molecular signaling play a role in organ development,” said Ophir Klein, MD, PhD, Executive Director of Cedars-Sinai Guerin Children’s, where he is also the David and Meredith Kaplan Distinguished Chair in Children’s Health, and co-corresponding author of the study.
Mechanical Pressure in Organizing Cells
The study, published in Nature Cell Biology, shows that as cells grow in the embryonic incisor tooth, they feel the growing pressure and use this information to organize themselves. “It’s like those toys that absorb water and grow in size,” said Neha Pincha Shroff, PhD, a postdoctoral scholar in the School of Dentistry at UCSF, and co-first author of the study. “Just imagine that happening in a confined space. What happens in the incisor knot is that the cells multiply in number in a fixed space and this causes a pressure to build up at the center, which then becomes a cluster of specialized cells.” Like people in a crowded bar, cells in the tissue start feeling the squeeze from their peers. The researchers found that the cells feeling the stronger pressure stop growing and start sending signals to organize the other surrounding cells in the tooth. They were literally pressed into becoming the tooth organizer.
“We were able to use microdroplet techniques that our lab previously developed to figure out how the buildup of mechanical pressure affects organ formation,” said co-corresponding author of the study Otger Campàs, Ph.D., who is currently Managing Director, Professor and Chair of Tissue Dynamics at the Physics of Life Excellence Cluster of TU Dresden, and former Associate Professor of Mechanical Engineering at UCSB. “It is really exciting that tissue pressure has a role in establishing signaling centers. It will be interesting to see if or how mechanical pressure affects other important developmental processes.”
Embryos use several of these signaling centers to guide cells as they form tissues and organs. Like building skyscrapers or bridges, sculpting our organs involves tight planning, a lot of coordination, and the right structural mechanics. Failure in any of these processes can be catastrophic when it comes to building a bridge, and it can also be damaging for us when growing in the womb.
“By understanding how an embryo forms organs, we can start to ask questions about what goes wrong in children born with congenital malformations,” said Ophir Klein. “This work may lead to additional research into how birth defects are formed and can be prevented.”
Reference: “Proliferation-driven mechanical compression induces signalling centre formation during mammalian organ development” by Neha Pincha Shroff, Pengfei Xu, Sangwoo Kim, Elijah R. Shelton, Ben J. Gross, Yucen Liu, Carlos O. Gomez, Qianlin Ye, Tingsheng Yu Drennon, Jimmy K. Hu, Jeremy B. A. Green, Otger Campàs and Ophir D. Klein, 3 April 2024, Nature Cell Biology.
DOI: 10.1038/s41556-024-01380-4
The study was funded by the National Institute of Dental and Craniofacial Research (OK and OC) in the USA, the Deutsche Forschungsgemeinschaft under Germany’s Excellence Strategy, and the Cluster of Excellence Physics of Life of TU Dresden (OC).
News
New nanomedicine wipes out leukemia in animal study
In a promising advance for cancer treatment, Northwestern University scientists have re-engineered the molecular structure of a common chemotherapy drug, making it dramatically more soluble and effective and less toxic. In the new study, [...]
Mystery Solved: Scientists Find Cause for Unexplained, Deadly Diseases
A study reveals that a protein called RPA is essential for maintaining chromosome stability by stimulating telomerase. New findings from the University of Wisconsin-Madison suggest that problems with a key protein that helps preserve chromosome stability [...]
Nanotech Blocks Infection and Speed Up Chronic Wound Recovery
A new nanotech-based formulation using quercetin and omega-3 fatty acids shows promise in halting bacterial biofilms and boosting skin cell repair. Scientists have developed a nanotechnology-based treatment to fight bacterial biofilms in wound infections. The [...]
Researchers propose five key questions for effective adoption of AI in clinical practice
While Artificial Intelligence (AI) can be a powerful tool that physicians can use to help diagnose their patients and has great potential to improve accuracy, efficiency and patient safety, it has its drawbacks. It [...]
Advancements and clinical translation of intelligent nanodrugs for breast cancer treatment
A comprehensive review in "Biofunct. Mater." meticulously details the most recent advancements and clinical translation of intelligent nanodrugs for breast cancer treatment. This paper presents an exhaustive overview of subtype-specific nanostrategies, the clinical benefits [...]
It’s Not “All in Your Head”: Scientists Develop Revolutionary Blood Test for Chronic Fatigue Syndrome
A 96% accurate blood test for ME/CFS could transform diagnosis and pave the way for future long COVID detection. Researchers from the University of East Anglia and Oxford Biodynamics have created a highly accurate [...]
How Far Can the Body Go? Scientists Find the Ultimate Limit of Human Endurance
Even the most elite endurance athletes can’t outrun biology. A new study finds that humans hit a metabolic ceiling at about 2.5 times their resting energy burn. When ultra-runners take on races that last [...]
World’s Rivers “Overdosing” on Human Antibiotics, Study Finds
Researchers estimate that approximately 8,500 tons of antibiotics enter river systems each year after passing through the human body and wastewater treatment processes. Rivers spanning millions of kilometers across the globe are contaminated with [...]
Yale Scientists Solve a Century-Old Brain Wave Mystery
Yale scientists traced gamma brain waves to thalamus-cortex interactions. The discovery could reveal how brain rhythms shape perception and disease. For more than a century, scientists have observed rhythmic waves of synchronized neuronal activity [...]
Can introducing peanuts early prevent allergies? Real-world data confirms it helps
New evidence from a large U.S. primary care network shows that early peanut introduction, endorsed in 2015 and 2017 guidelines, was followed by a marked decline in clinician-diagnosed peanut and overall food allergies among [...]
Nanoparticle blueprints reveal path to smarter medicines
Lipid nanoparticles (LNPs) are the delivery vehicles of modern medicine, carrying cancer drugs, gene therapies and vaccines into cells. Until recently, many scientists assumed that all LNPs followed more or less the same blueprint, [...]
How nanomedicine and AI are teaming up to tackle neurodegenerative diseases
When I first realized the scale of the challenge posed by neurodegenerative diseases, such as Alzheimer's, Parkinson's disease and amyotrophic lateral sclerosis (ALS), I felt simultaneously humbled and motivated. These disorders are not caused [...]
Self-Organizing Light Could Transform Computing and Communications
USC engineers have demonstrated a new kind of optical device that lets light organize its own route using the principles of thermodynamics. Instead of relying on switches or digital control, the light finds its own [...]
Groundbreaking New Way of Measuring Blood Pressure Could Save Thousands of Lives
A new method that improves the accuracy of interpreting blood pressure measurements taken at the ankle could be vital for individuals who are unable to have their blood pressure measured on the arm. A newly developed [...]
Scientist tackles key roadblock for AI in drug discovery
The drug development pipeline is a costly and lengthy process. Identifying high-quality "hit" compounds—those with high potency, selectivity, and favorable metabolic properties—at the earliest stages is important for reducing cost and accelerating the path [...]
Nanoplastics with environmental coatings can sneak past the skin’s defenses
Plastic is ubiquitous in the modern world, and it's notorious for taking a long time to completely break down in the environment - if it ever does. But even without breaking down completely, plastic [...]
