SAN FRANCISCO, Aug. 22 (UPI) -- By studying hundreds of mutant mice with two upper jaws, researchers have uncovered new insights on the genes that make up the jaw in everything from humans to lizards.
The researchers hope their findings will help study birth defects, because roughly one-third of all such afflictions involve some aspect of the head. Cleft palates and lips, for instance, affect roughly one in every 700 to 1,000 newborns in the United States.
"A clearer understanding of how the skull is put together, through genetic analyses in mice, fish and other experimental organisms, will help us understand what causes such malformations and possibly help prevent or cure them," researcher Michael Depew, a developmental biologist at the University of California at San Francisco, told United Press International.
Jawed vertebrates diverged from their jawless relatives more than 400 million years ago. Since then, the researchers said jaws have proved one of the most important events in vertebrate evolution, allowing "gnathostomes" -- Greek for "jawed mouth" -- to chew their way everywhere around the world, while only a few jawless fishes such as lampreys remain today.
The evolution of the jaw raises great controversy among scientists due to its complicated nature. Investigators often concentrate on outgrowths of tissue known as branchial arches, structures present only in the embryonic stages in the front of the neck and lower head that contribute to making gills and the mouth. "In most vertebrates, the first arch contributed to the jaw apparatus," co-researcher John Rubenstein said.
Because the jaw's origin might have been only cartilaginous arches, scientists theorize there have been a number of ways historically of attaching jaws to the head. "Some animals attach their jaw directly to the skull, whereas others do so indirectly," Depew explained.
In lampreys, for example, unlike jawed vertebrates the cartilage that the branchial arches form is uniform and not segmented. Prior studies showed the lampreys' Dlx genes, which help control brain and appendage development, are expressed mostly the same way throughout the branchial arches.
In their paper, which appears in the journal Science's Aug. 22 online issue, Depew and Rubenstein said they sought to uncover the genetic mechanisms that generate all the interlocking parts of the jaw across all gnathostomes. They looked at mutant mice that had upper jaws in place of where there lower jaws normally would be.
When the researchers disrupted some of these genes in mice, it led to mice with two upper jaws. This outcome revealed the Dlx genes in jawed animals provide identities to the segments within the branchial arches by turning on in precise patterns. Rubenstein and Depew wrote that the evolution from a jawless to a jawed life coincided with the genetic modifications of this pattern.
The discovery of these mechanisms could help explain some mysteries in mammalian evolution. Two of the three bones in the ear actually derive from ancient jaw articulation bones. Although such a change may seem complex, "it's not perhaps mystical," Depew said, and instead may follow stepwise transitions in these genes.
James Langeland, assistant professor of biology at Kalamazoo College in Michigan said, "This is the first evidence that Dlx genes are clearly involved in the formation of the jaw ... clearly one would expect that some human birth defects may be linked to these genes."
Langeland added that a comparative study of these genes across a number of vertebrates likely would prove valuable for understanding jaw evolution.
(Reported by Charles Choi, UPI Science News, in New York)
