Scientists have captured the first instance of an early stage embryo forming, 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 themselves into the earliest form of the heart and the first phase of its spine and brain, called the ‘neural tube.’
An innovative technique using fluorescent protein was employed 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 the human kind in these early phases, researchers now plan to study in real-time what early missteps by these embryonic cells lead to birth defects, in order to help improve future treatments 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 protein was employed to illuminate this tiny embryo
The researchers – molecular bio-scientists from 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, stills of the embryo’s early spine and brain formation
Above, later still images from the embryo’s early spine and brain formation
Roughly 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 surgeries that place just days after birth, but in worse cases transplants for heart defects may be needed.
Scientists from the University of Queensland created a genetically engineered quail embryo that formed while also producing a reflective fluorescent protein called Lifeact.
The genes for creating these Lifeact proteins were implanted into the live quail embryo via direct injection into its blood-circulating primordial germ cells.
‘Avian [meaning birds, like quail] embryos are an excellent model of human development,’ according to Dr Melanie White, but especially in these early phases 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 technology to peer through and leave undisturbed.
‘It is very difficult to film these stages of embryonic development as they occur after human embryos have implanted into the mother’s womb,’ Dr White explained.
‘Because quails grow in an egg they’re very accessible for imaging,’ she noted, ‘and their early development is very similar to a human at the time the [human] embryo implants in the uterus.’
Above, the glow of the fluorescent proteins revealed the embryo’s early scaffolding, called the ‘actin cytoskeleton,’ which gives cells shape and helps them move. The fluorescent proteins bond 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 cling to and helps them move.
These fluorescent proteins bonded selectively 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 arm-like protrusions on individual cells (lamellipodia and filopodia), which help the cells crawl along the cytoskeleton’s protein supports into the right place.
Dr White and her colleagues documented heart stem cells deep inside the embryo as they climbed into position on this cytoskeleton to craft 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 are missing is the dynamic information of how the embryo coordinates the movement, positioning and fate of its cells to move from one stage to the next,’ as Dr White explained the purpose of the new videos to Newsweek.
‘This information can only be obtained using live imaging approaches where we can track how the 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 largely a mystery,’ according to Dr White.
One of the other crucial events documented by the Queensland team’s technique was the ‘zipping up’ of cells along the long open edges of the embryo’s neural tube.
Like a burrito or wrap, the cells fold into this tube-like shape and seal into a tube with a zipper-like motion as the cells’ small arm-like lamellipodia and filopodia link up.
Once closed off, this newly formed neural tube will continue to grow and mature into its future shape as the brain and spinal cord.
‘We saw how the cells reached across the open neural tube with their protrusions to contact the opposite side,’ Dr White said.
‘The more protrusions the cells formed, the faster the tube zipped up.’
Above, an image shows the ‘zipper’ motion as the embryo’s ‘neural tube’ is formed by each cell’s arm-like protrusions – its lamellipodia and filopodia – grabbing hold of each other
Above, the researchers were able to record the formation of arm-like protrusions on individual cells – which help the cells crawl along the cytoskeleton’s protein supports into the right place. In the above image, the cell’s arms link up to close the neural tube walls.
It is exactly this process, she said, that often ‘goes awry or is disrupted’ during the fourth week of human development — leading to congenital birth defects of the brain or spine, whether inherited or induced by environmental factors.
‘Our aim is to find proteins or genes that can be targeted in the future or used for screening for congenital birth defects,’ Dr White said.
‘We are very excited at the possibilities that this new quail model now offers to study development in real time,’ the researcher, who also heads the Dynamics of Morphogenesis Lab at Queensland’s Institute for Molecular Biosciences, said.
Dr White and her team’s work was published this June in the Journal of Cell Biology.
‘In our lab, we are now building on the initial experiments we have 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 deficits) disrupt this development and lead to congenital defects.’