Quail Embryos Illuminate Human Birth Defects

Quails are small, plump birds that scurry through grasslands on foot rather than take to the skies. Unexpectedly, studying these ground-dwellers has helped scientists uncover clues about a type of congenital defect in humans.

“In human embryos, neural tube development is quite similar to [that in quail] embryos,” explained Siew Zhuan Tan, a developmental biologist and research assistant in the lab of University of Queensland cell biologist Melanie White.

The development of the neural tube—the embryonic precursor to the brain and spinal cord—going awry results in severe birth defects. Such neural tube defects affect nearly 300,000 babies worldwide each year, with the most common types of this condition resulting in parts of the brain or spinal cord being exposed at birth.¹

Since the defects happen in fetuses within the first month of pregnancy often before a person knows they are pregnant, the condition is technically challenging to study in human embryos. Given the similarity in neural tube development in humans and quails, the animal model comes in handy in investigating this process

By using confocal microscopy, White, Tan and their colleagues image quail embryos, shedding light on the molecular dynamics involved in neural tube development.² This could offer crucial information about potential therapeutic targets and genes to screen for predicting neural tube defects

Tan begins studying these structures by dissecting quail embryos, fixing them, and embedding them in a gelling material like agarose. This is where she usually encounters her first challenge. “I need a high percentage of agarose in order to make sure the sample is intact,” said Tan. “And with a high percentage of agarose, it will solidify quite quickly.”

So, she races against time to ensure that the fixed tissue sits comfortably within the gel before it solidifies. She also has to ensure that the sample does not detach from the gel, so she performs whole-mount immunostaining with fluorescent antibodies on the intact sample to prevent separation between the sample and gel on more fragile cut sections. Once this step is done, she slices the tissue to obtain sections almost as thin as a human hair. This ensures that the tissue is thin enough to acquire meaningful signals upon peeking into it using a confocal microscope.

This usually results in stunning images highlighting the transcriptional regulators and molecules that drive vertebrate neural tube formation. For instance, looking at alpha tubulins has offered insight into the structural scaffold that aids cell elongation and division, which is crucial in neural tube formation. In another image, which looked like an angel under the microscope, Tan observed filamentous actin and cells expressing a transcription factor controlling their fate towards notochord development. Having pored over the literature to standardize the imaging pipeline for the lab, Tan feels particularly satisfied seeing the vivid images. “To me [the images] are nice and beautiful,” said Tan.