By Edwin L. Aguirre
Cleft lip and cleft palate are birth defects that occur when a baby’s lip or mouth do not form properly during pregnancy. About 1 in every 1,600 babies is born with these defects in the United States, according to the Centers for Disease Control and Prevention.
Children with these debilitating conditions often experience problems with feeding, teeth development, speaking and hearing as well as loss of self-esteem.
Thanks to a pair of three-year grants totaling more than $612,000 from the National Institute of Dental and Craniofacial Research, Asst. Prof. Jennifer L. Fish
of the Department of Biological Sciences
is conducting studies to understand how genetic mutations cause cleft lips and palates and other birth defects of the head, face and mouth.
She wants to know the molecular and cellular mechanisms responsible in patients who have mutations in their genes, and why the severity of the defects varies from individual to individual.
“In some patients the defects are more severe than in others, and we want to find out why that variation exists,” says Fish, who is the sole principal investigator for the two projects. “Such variation contributes to difficulties in the diagnosis and treatment of craniofacial malformations.”
The first grant, worth nearly $456,000, will be used to conduct research on how mutations in the gene called SATB2
can lead to cleft palate, very small lower jaw, dental abnormalities and low bone density.
“We will investigate normal bone development and how mutations in SATB2 disrupt this process to cause defects,” says Fish.
The second grant, worth more than $156,000, will fund research into how reduction in the levels of the FGF8 gene during facial bone growth and gland development contributes to craniofacial disorders.
According to Fish, FGF8 is an important gene expressed in the pharyngeal pouches, which are transient structures in embryos that develop into the thymus, thyroid and parathyroid glands and contribute to the formation of eardrums and tonsils and the proper development of the facial skeleton.
“Our goal is to investigate how FGF8 expression regulates the development of pharyngeal pouches,” she says. “This is important since pharyngeal pouches have not been studied extensively in mammals before. Reductions in FGF8 during development of the embryo are associated with craniofacial disorders.”
Assisting Fish in the lab work are postdoctoral researcher Evelyn Schwager, Ph.D. student Nate Zbasnik and master’s student Adeeba Nahrin, as well as biology undergraduates Huy Nguyen, Marcelo Costa and Analise Loreus.
Although Fish’s research efforts will not lead to new diagnostic tools for the early detection of the deformities before a child is born (which can be done through genetic screening in the lab), they aim to improve researchers’ understanding of the role of genetic mutations and potentially lead to the development of treatment options for craniofacial and bone defects.