Oregon researchers discover a mechanism leading to cl...( By creating a genetic mutation in ze...),Health

By creating a genetic mutation in zebrafish, University of Oregon scientists say they've discovered a previously unknown mechanism for cleft palate, a common birth defect in humans that has challenged medical professionals for centuries.

Many molecular pathways in zebrafish are present in humans and other vertebrates. By studying the induced mutation in zebrafish, the 10-member research team isolated a disruption in early developmental signaling involving Pdgf, a platelet-derived growth-factor protein, and a microRNA known as Mirn140, the researchers write in a paper posted online in advance of regular publication the monthly journal Nature Genetics.

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. It came as a surprise that zebrafish into which the investigators had injected too much Mirn140 also had cleft palate.

MicroRNAs are small gene products, found to be involved in gene expression, that were first described in 1993 by researchers at Harvard University. The term microRNA was introduced in when these single-strand RNA molecules about nucleotides in length were more fully detailed in Science in October 2001 by Gary Ruvkun of Massachusetts General Hospital in Boston.

Mirn140, when operating normally, allows for normal cell signaling by the Pdgfra protein that properly triggers cell migrations necessary for correct oral-cranial building. The researchers showed that Mirn140 blocks the cell’s expression of Pdgfra. Thus, cleft palate can 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," said principal investigator John H. Postlethwait, a professor of biology and member of the UO's Institute of Molecular Biolog
'/>"/>