Scientists have captured the first example of an embryo forming at an early stage, which could help solve the ‘mystery’ of how congenital birth defects start in humans.
Australian researchers watched in amazement as the cells of a quail embryo crawled around its protein-based support structure – organizing into the earliest form of a heart and the first stage of its spine and brain, called a ‘neural tube’ .
An innovative technique using fluorescent proteins was used to illuminate these cells within the tiny embryo as the team recorded its early moments taking shape.
Because of the quail embryo’s similarity to humans at these early stages, the researchers now plan to study in real time what early mistakes from these embryonic cells lead to birth defects in order to help improve treatments. future for people.
For the first time ever, scientists have recorded real-time video of an early-stage embryo forming the ‘neural tube’ that will grow to become its brain and spinal cord (above). An innovative technique using fluorescent proteins was used to illuminate this tiny embryo
The researchers – molecular bioscientists from the University of Queensland in Australia – report that these new videos may soon help modern medicine understand congenital birth defects and how to correct them. Above, pictures of the early embryonic spine and brain formation
Above, later images from the early embryonic spine and brain formation
About three percent of all human babies are born with congenital birth defects, the study’s lead author said, most commonly heart defects and neural tube defects.
The only treatments available are operations that take place just days after birth, but in the worst cases transplants may be needed for heart defects.
Scientists from the University of Queensland created a genetically engineered quail embryo that was formed by also producing a reflective fluorescent protein called Lifeact.
The genes for making these Lifeact proteins were implanted into the living quail embryo via direct injection into its circulating primitive blood cells.
‘Birds [meaning birds, like quail] embryos are an excellent model of human development,’ according to Dr Melanie White, but especially in these early stages of growth.
“The development of many major organs including the heart and the neural tube (which goes on to form the brain and spinal cord) is very similar,” she said.
Quail embryos are also easier to record alive as they grow, because the thin shell of an egg is easier for medical tech to see and remove without disturbing.
“It is very difficult to film these stages of embryonic development as they occur after human embryos are implanted in the womb,” explained Dr White.
“Because quail grow in an egg, they are very accessible for imaging,” she noted, “and their early development is very similar to a human at that time. [human] embryo implants in the uterus.’
Above, the glow of fluorescent proteins revealed the embryo’s early scaffolding, called the ‘actin cytoskeleton’, which gives shape to cells and helps them move. Fluorescent proteins bind selectively to actin, also a protein, giving definition to 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 grip and helps them move.
These fluorescent proteins selectively bound to actin, which is also a protein, lighting up and giving definition to this early embryonic structure.
With this illumination, the researchers were able to record the formation of wing-like protrusions on individual cells (lamellipodia and filopodia), which help cells crawl along cytoskeletal protein supports in the right place.
Dr White and her colleagues documented heart stem cells deep within the embryo as they moved into position on this cytoskeleton to create the early heart.
“It is the first time anyone has captured the actin cytoskeleton of a cell facilitating this contact in live imaging,” Dr White said in a statement.
“One of the main 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 another,” as Dr White explained to Newsweek the purpose of the new videos.
“This information can only be obtained using live imaging approaches where we can track how embryonic tissue changes over time,” she said.
“How cells interact with each other and move in real time to organize into complex tissues in the forming embryo is still a mystery,” according to Dr White.
One of the other important events documented by the Queensland team’s technique was the ‘compaction’ of cells along the long open ends of the embryo’s neural tube.
Like a burrito or wrap, the cells fold into this tube-like shape and close into a tube in a zipper-like motion as the lamellipodia and filopodia of the small arm-like cells connect.
Once closed, this newly formed neural tube will continue to grow and mature into its future form as the brain and spinal cord.
“We saw how the cells reached through the open neural tube with their extensions to contact the opposite side,” Dr White said.
“The more protrusions the cells form, the faster the tube zips.”
Above, an image shows the ‘zinc’ moving as the embryo’s ‘neural tube’ is formed by each cell’s wing extensions – its lamellipodia and filopodia – grasping each other.
Above, the researchers were able to record the formation of wing-like protrusions on individual cells – which help the cells crawl along the cytoskeletal protein supports in the right place. In the image above, the arms of the cell connect to close the walls of the neural tube.
It is this very process, she said, that often ‘goes awry or breaks down’ during the fourth week of human development – leading to congenital defects of the brain or spine, whether inherited or induced by environmental factors.
“Our goal is to find proteins or genes that can be targeted in the future or used to screen for congenital birth defects,” said Dr White.
“We are very excited about the opportunities this new quail model now offers to study development in real time,” said the researcher, who also directs the Dynamics of Morphogenesis Laboratory at the Queensland Institute for Molecular Biosciences.
The work by Dr White and her team was published this June in the Journal of Cell Biology.
“In our lab, we’re now building on the initial experiments we’ve done to try to understand how the heart and neural tube form in real time,” she said.
Specifically, Dr White’s team is now “studying how mutations identified in patients or maternal factors (diabetes, nutritional deficiencies) disrupt this development and lead to congenital defects.
