Chicken embryos illuminate cleft palate problems

For Dr. Joy Richman eggs offer an untold wealth of information about human development.

A pediatric dentist and development biologist, Richman studies chicken embryos, focusing on the intricately patterned facial bones and limbs.

“The embryonic faces of vertebrates including humans, mice and chickens are very similar,” says Prof. Richman who teaches in the Faculty of Dentistry.

Her lab investigates the molecules that tell the initially indistinct cells in the embryo to form recognizable structures such as the skeleton of the jaw or hand. By tweaking molecules at an early stage it is possible to duplicate structures or transform one part of the embryo into another. Richman’s study on embryo patterning was recently awarded more than $900,000 from the Canadian Institutes of Health Research (CIHR).

She explains that face development for all mammalian embryos begins with discrete buds of tissues – called prominences – that surround the primitive oral cavity. These grow together to form the face.

Currently, one in 700 babies is born with a cleft lip or palate. For a variety of genetic and environmental reasons, the separate areas of the face do not join together as they would normally, resulting in a cleft.

Many times, facial defects are accompanied by limb or digit abnormalities, both of which require multiple surgeries, often followed by expensive dental or orthopedic treatments.

Given the intricacies of human embryos and the serious consequences of anomalies, Richman says it is important to study a model organism that mirrors human development yet can be accessed during embryonic development.

“The chicken embryo is ideal to unravel these mysteries.”

To view what is happening in the chicken embryo, Richman cuts a window the size of a postage stamp into the eggshell. When researchers place the egg under the microscope, they can see the beating red heart, the face and limbs.

In work leading up to the CIHR grant, Richman traced jaw development to the presence of retinoic acid, a vitamin A derivative and a protein linked to bone formation.

By inserting tiny beads containing these molecules into the early chicken embryo, Richman found that the cheek bones were replaced with bones that normally are found in the centre of the face, essentially duplicating the upper beaks.

The experiment on beak duplication also led Richman to her current work which is to investigate the genes that make the centre of the face. Out of hundreds of genes involved in this process, one in particular caught her attention.

“This gene piqued my interest because it makes a protein that is secreted outside the cell and as such could play a pivotal role,” says Richman. “It may act as an “orchestrator” directing nearby cells into required patterns.”

She says the majority of studies on face development seek to unlock the secrets within the cell, looking at which gene levels are up or down. However, far fewer people are looking at what is happening outside the cells.

“It seems to me that we also need to understand what is happening in the stage between the genes changing and the first signs of the skeleton appearing.”

Findings to date support her theory about the importance of an “orchestrator.” Richman discovered that the protein was strongly turned on in during the chicken embryo’s beak development. She also found that placing the gene for this protein into the embryo caused it to grow an extra beak and also to duplicate digits of the limb.

“We now want to manipulate the levels of this protein in the early chicken embryo to determine its roles in shaping the skeleton of the limbs and face.”

Study results will aid those yet unborn, says Richman. “Our work will shed light on inherited birth defects that affect the skeleton including cleft lip, jaw size and shape abnormalities and disturbances in the bones of the hands and feet.

She adds, “Our results may also one day help to improve healing after injuries to the skeleton.”

Dr.  Joy Richman cuts a window the size of a postage stamp into the eggshell to observe face and limb development.

pictured below: A 13-day chicken embryo whose skull and leg show extra beak parts and extra toes (indicated by arrows) produced by the introduction of a foreign gene.