Scientists have captured the first example of an early-stage embryo, which could help solve the “mystery” of how birth defects begin in humans.
Australian researchers watched in amazement as cells in a quail embryo crawled around their protein-based support structure, organizing themselves into the earliest form of the heart and the first stage of its spinal column and brain, called the “neural tube.”
An innovative technique using fluorescent protein was used to illuminate these cells inside the tiny embryo as the team recorded their first moments of formation.
Because of the similarity of the quail embryo to humans in these early stages, researchers now plan to study in real time what early errors in these embryonic cells lead to birth defects, in order to help improve future treatments for people.
For the first time, scientists have recorded a real-time video of an early-stage embryo forming the “neural tube” that will grow into its brain and spinal cord (above). An innovative technique using fluorescent protein was used to illuminate this tiny embryo.
The researchers, molecular biology scientists at the University of Queensland in Australia, report that these new videos could soon help modern medicine understand congenital birth defects and how to correct them. Above, images of the early formation of the embryo’s spine and brain
Above, later still images of the initial formation of the embryo’s spine and brain.
About three percent of all human babies are born with birth defects, the study’s senior author said, most commonly heart defects and neural tube defects.
The only treatments available are surgeries performed a few days after birth, but in the worst cases transplants may be needed to correct heart defects.
Scientists at the University of Queensland created a genetically modified quail embryo that formed at the same time as it produced a reflective fluorescent protein called Act of life.
The genes to create these Lifeact proteins were implanted into the live quail embryo by direct injection into its primordial germ cells circulating in the blood.
“Avian embryos (i.e. birds, such as quail) are an excellent model for human development,” according to Dr. Melanie White, but especially in these early stages of growth.
“The development of many important organs, including the heart and the neural tube (which later forms the brain and spinal cord), is very similar,” he said.
Quail embryos are also easier to record alive as they grow, because the thin egg shell allows medical technology to more easily look through it and leave it intact.
“It is very difficult to film these stages of embryonic development because they occur after the human embryos have implanted in the mother’s uterus,” Dr. White explained.
“Because quails grow in an egg, they are very accessible for imaging,” he noted, “and their early development is very similar to that of a human by the time the (human) embryo implants in the uterus.”
Above, the glow of fluorescent proteins revealed the embryo’s early scaffolding, called the “actin cytoskeleton,” which gives cells shape and helps them move. The fluorescent proteins selectively bind to actin, also a protein, defining this early embryonic structure.
The glow of these fluorescent proteins revealed the embryo’s early protein scaffolding, called the “actin cytoskeleton,” which gives its cells a shape to attach to and helps them move.
These fluorescent proteins selectively bound to actin, which is also a protein, illuminating and giving definition to this early embryonic structure.
Using this illumination, the researchers were able to record the formation of arm-like protrusions on individual cells (lamellipodia and filopodia), which help cells crawl along the protein supports of the cytoskeleton to the right place.
Dr. White and her colleagues documented heart stem cells deep within the embryo as they rose to their position in this cytoskeleton to create the early heart.
“It’s the first time anyone has captured the cell’s actin cytoskeleton, facilitating this contact in live imaging,” Dr. White said in a statement.
“One of the key things we’re missing is dynamic information about how the embryo coordinates the movement, positioning and fate of its cells to move from one stage to the next,” Dr. White said of the purpose of the new videos. Week of news.
“This information can only be obtained using live imaging, where we can track how embryonic tissue changes over time,” he said.
“How cells interact with each other and move in real time to organize themselves into complex tissues in the forming embryo remains largely a mystery,” said Dr. White.
One of the other crucial events documented by the Queensland team’s technique was the closure of cells along the long, open edges of the embryo’s neural tube.
Like a burrito or a wrap, the cells fold into a tube shape and seal into a tube with a zipper-like motion as the cells’ tiny, arm-like lamellipodia and filopodia snap together.
Once closed, this newly formed neural tube will continue to grow and mature until it reaches its future form: the brain and spinal cord.
“We watched the cells push through the open neural tube with their protrusions to come into contact with the opposite side,” Dr. White said.
‘The more protrusions the cells formed, the faster the tube closed.’
Above, an image shows the “zipper” movement as the embryo’s “neural tube” is formed by the arm-like protrusions of each cell (its lamellipodia and filopodia) grasping each other.
In the image above, the researchers were able to record the formation of arm-like protrusions on individual cells, which help the cells to move along the protein supports of the cytoskeleton to the right place. In the image above, the arms of the cells come together to close the walls of the neural tube.
It is exactly this process, he said, that often “goes awry or is disrupted” during the fourth week of human development, leading to birth defects of the brain or spine, whether inherited or induced by environmental factors.
“Our goal is to find proteins or genes that can be studied in the future or used to detect birth defects,” Dr. White said.
“We are very excited about the possibilities that this new quail model now offers for studying development in real time,” said the researcher, who also heads the Morphogenesis Dynamics Laboratory at the Queensland Institute for Molecular Biosciences.
The work of Dr. White and her team was published in June in Journal of Cell Biology.
“In our lab, we are now leveraging the initial experiments we’ve done to try to understand how the heart and neural tube form in real time,” he said.
Specifically, Dr. White’s team is now “studying how mutations identified in patients or maternal factors (diabetes, nutritional deficiencies) alter this development and lead to birth defects.”