Zebrafish study reveals previously unknown mechanism for cleft palate

London, Feb 17 : Researchers at the University of Oregon have discovered a previously unknown mechanism for cleft palate, a common birth defect often seen in humans, by creating a genetic mutation in zebrafish.

The new findings attain significance because many molecular pathways in zebrafish are present in humans and other vertebrates.

During the study, the 10-member research team isolated a disruption in early developmental signalling involving a platelet-derived growth-factor protein called Pdgf, and a microRNA known as Mirn140.

The researchers reported that mutant zebrafish lacking Pdgf had cleft palate similar to many human babies, showing that this growth factor helps to organize cells that make the palate.

They also found that zebrafish into which too much Mirn140 was injected also had cleft palate.

When operating normally, Mirn140 allows for normal cell signalling by the Pdgfra protein that properly triggers cell migrations necessary for correct oral-cranial building.

Based on their observations, the researchers concluded that cleft palate might result from too little Pdgfra that occurs because of either a mutation in the Pdgfra gene or too much Mirn140.

"We showed that this microRNA regulates the expression of the gene by controlling the migration of precursor cells to the palate-forming area. This is a novel mechanism never before described," Nature quoted principal investigator John H. Postlethwait, a professor of biology and member of the UO's Institute of Molecular Biology and Institute of Neuroscience, as saying. The researchers said that the study provides a new window into the mechanisms involved in cleft palate and craniofacial defects, but they have warned that the findings don't point toward new clinical applications.

"Further exploration of how microRNAs and other factors modulate signaling pathways such as the Pdgf pathway during palatogenesis will assuredly continue to provide insights into the cause of, and possible treatments for, human craniofacial disease," the authors said.

The study is published online in the journal Nature Genetics.

ANI