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A recent study published by researchers at the 91ֱ����Ƶ and the University of Heidelberg in Germany has identified a key aspect of fetal development that may be critical for preventing common fetal congenital conditions. 

The paper, titled “Primary Cilia are Critical for Tracheoesophageal Septation,” which was published in the journal Developmental Dynamics in late September, has found that small antennae-like structures found on the surface of cells, known as primary cilia, play a crucial role in directing how our cells align, separate, and divide to ensure normal development of the trachea and esophagus in humans.  

The research, led by 91ֱ����ƵCollege of Osteopathic Medicine's Lindsey Avery Fitzsimons, Ph.D., a postdoctoral research fellow and adjunct instructor, and 91ֱ����ƵCOM's Kerry L. Tucker, Ph.D., associate professor, found that a genetic mutation, resulting in the loss of primary cilia in mouse embryos, prevents complete separation of the trachea and esophagus during fetal development, leading to the formation of a birth defect known as a tracheoesophageal fistula, or TEF. 

This kind of congenital condition, commonly seen in the lower respiratory tract of newborns, significantly affects a child’s ability to breathe and feed independently, Fitzsimons said. It also increases the likelihood that a newborn will develop frequent lung infections.  

TEF is also one of the hallmark congenital disorders seen in cases of VACTERL association, which affects the development of the trachea and esophagus along with many other essential organs in the body. According to research published in the Orphanet Journal of Rare Diseases, about 1 in 10,000 live births are affected by this condition, where infants are born with three or more congenital disorders in specific parts of the body, such as the anus, heart, trachea, esophagus, kidneys, or limbs.  

“The primary cilium is becoming more and more relevant to medicine and an important variable to consider in all biomedical research seeking to understand how and why cells behave and respond to their surrounding environment,” said Fitzsimons.  

Tucker, a researcher in UNE's Center for Excellence in the Neurosciences, said that while research currently exists surrounding primary cilia in humans, little of it focuses specifically on VACTERL association.  

“Problems with the development of the trachea and esophagus are not uncommon,” Tucker said. “If we can come up with the means of understanding how they arise at the developmental level, the more likely we are to be able to prevent or better treat congenital anomalies as they arise in newborns and in children.” 

Prior research in the field found that primary cilia are involved in organizing cell and organ formation during development, into adulthood, and especially in the development of an increasing number of common diseases such as osteoarthritis and high blood pressure. 

“By discovering that primary cilia are controlling the formation of developmental defects like TEF and VACTERL, we are providing evidence to support the feasibility and viability of using these structures in the development of medications, genetic screenings, and other therapeutic targets for the treatment and prevention of medical conditions both addressing these and beyond these difficult birth conditions,” Fitzsimons said. 

A large number of FDA-approved medications are already designed to target the function of the primary cilium, mostly for cancer patients. These medications have shown promising results from clinical trials research, she said, adding that she hopes the use of existing drug therapies for the development of non-invasive treatments will continue to be prioritized in biomedical research. 

This research has the potential to impact the prevention and treatment of conditions that affect these vital organs, Tucker added, ultimately improving the health and well-being of individuals born with such congenital disorders. 

“We have taken a significant stride towards making a positive impact in addressing this healable condition,” Tucker said. “By unraveling the complexities of the primary cilium, we can make considerable headway in the field of medicine and provide a healthier future for affected individuals.”