Home | Genetics and Birth Defects | SickKids scientists use a common pet-store fish to reel in a deeper understanding of birth defects and genetic disorders

SickKids scientists use a common pet-store fish to reel in a deeper understanding of birth defects and genetic disorders

Zebrafish are known as common aquarium fish because they are small, abundant and easily grown.

They are also transparent, so while you can’t watch a human baby grow inside its mother, this is actually possible in a zebrafish. These are just some of the reasons why these fish are popular with scientists, too.

Scientists at The Hospital for Sick Children (SickKids) have been using zebrafish for several years to uncover clues to the normal development of the embryo. Embryonic development is a very precise growing process; any missteps at this stage can lead to birth defects and disease. One of the key regulators in the normal development of the embryo is the primary cilium. Almost every cell in the human body forms a primary cilium, which is a hairlike structure on the surface of a cell. Cilia help move things around the cell by directing the flow of fluid surrounding cells. They also play a key role in organizing cells during development. Defects in cilia can result in polycystic kidney disease, certain types of cancers and genetic disorders.

In a study published in the March 21 edition of Nature Cell Biology, researchers used genetically-modified zebrafish to study cilia formation during embryonic development. The development of zebrafish is quite similar to that of humans. The scientists developed powerful techniques that allow them to watch cilia form and function in real time.

The researchers found that a pathway or network of proteins called planar cell polarity (PCP) play a key role in the organization of cilia. PCP signals tell cells where to go during the formation of tissue. In this study, scientists found that these PCP signals also instruct cells on where the cilia should form and what direction they should face. The location and orientation of the cilia dictate the flow of fluids around the cells.  

“Understanding the formation and role of cilia will give us a better picture of normal human embryo development and will shed light on new ways to approach developmental defects and genetic disorders,” says Dr. Brian Ciruna, Principal Investigator of the study and Scientist at SickKids, Assistant Professor in the Department of Molecular Genetics at the University of Toronto, and Canada Research Chair, Developmental Genetics and Cell Biology.

They found PCP signalling played an essential role in cilia positioning in the lining the spinal canal, the embryonic organizer (regions of the embryo that control development) and the pronephric duct (involved in the development of urinary and reproductive organs).  Neural tube defects such as spina bifida result from abnormal development of the spinal cord.  These types of defects are relatively common occurring in one out of 1,000 human pregnancies.   

Now that the researchers have identified this pathway, the next step is to go on a fishing expedition for other molecules that play a role in normal development.

The research was supported by the Terry Fox Foundation, the Natural Sciences and Engineering Research Council of Canada, the Canada Research Chairs program and SickKids Foundation.

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