Oregon researchers discover a mechanism leading to cleft palateFebruary 12, 2008By 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 Biology and Institute of Neuroscience. "This is a novel mechanism never before described." A cleft palate is an opening in the roof of the mouth in which the two sides of the palate did not fuse, or join together, during a baby's early development. Cleft palate can negatively affect speech production, feeding, maxillofacial growth and dentition. The first known attempt to correct the defect occurred in 500 A.D. The defect occurs with or without cleft lip (a separation of the two sides of the lip), on average, in 1 in 600 newborns, according to the Cleft Palate Foundation, but can vary by race. The highest incidence (3.6 per 1,000 births) occurs in American Indians. Palate formation begins after five weeks of gestation in humans and defects can become visible at 17 weeks, according to WebMD's eMedicine. The findings provide a new window into the mechanisms involved in cleft palate and craniofacial defects, but researchers caution 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 conclude. University of Oregon |
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| Related Cleft Palate Current Events and Cleft Palate News Articles In rare disease, a familiar protein disrupts gene function An international team of scientists studying a rare genetic disease discovered that a bundle of proteins with the long-established function of keeping chromosomes together also plays an important role in regulating genes in humans. Scientists discover why teeth form in a single row A system of opposing genetic forces determines why mammals develop a single row of teeth, while sharks sport several, according to a study published today in the journal Science. When completely understood, the genetic program described in the study may help guide efforts to re-grow missing teeth and prevent cleft palate, one of the most common birth defects. Advancement in tissue engineering promotes oral wound healing Oral tissue engineering for transplantation to aid wound healing in mouth (oral cavity) reconstruction has taken a significant step forward with a Netherlands-based research team's successful development of a gum tissue (gingival) substitute that can be used for reconstruction in the oral cavity. First trimester smoking linked to oral clefts Smoking during the first trimester of pregnancy is clearly linked with an increased risk of cleft lip in newborns. Moms' smoking linked to increased risk of birth defects Babies whose mothers smoked during pregnancy were more than twice as likely to have a cleft palate or lip as those whose mothers didn't, according to research results released today. Study finds genetic variant plays role in cleft lip University of Iowa researchers and collaborators have found, in a previously identified gene, a variation that likely contributes to one in five cases of isolated cleft lip. Genetic profile reveals susceptibility to cleft palate For the first time, researchers from the University of Pittsburgh School of Dental Medicine have identified a series of genetic mutations that appear to be linked to significant risk for cleft palate and other dental abnormalities. New insight into most common forebrain malformation St. Jude Children's Research Hospital scientists have identified one of the molecular mechanisms underlying the genetic brain malformation called holoprosencephaly (HPE). The findings not only yield insights into the most common developmental malformation of the anterior brain and face in newborns, but also help in understanding the intricate process by which the brain forms in the developing fetus. USC researchers identify alternate pathway that leads to palate development Researchers at the University Of Southern California School Of Dentistry have uncovered another clue behind the causes of cleft palate and the process that leads to palate formation. Lack of time on tummy shown to hinder achievement The American Physical Therapy Association (APTA) is urging parents and caregivers to ensure that babies get enough "tummy time" throughout the day while they are awake and supervised, in light of a recent survey of therapists who say they've noticed an increase in motor delays in infants who spend too much time on their backs while awake. More Cleft Palate Current Events and Cleft Palate News Articles |
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