Possible links to humans
In addition to the findings in flies, Akiyama found that mutations in the genes for making BMPs in humans that directly mirror the genetic code for making Gbb38 in flies, occur in people with cleft lip (with or without cleft palate), and the reproductive disorders premature ovarian failure and persistent Mullerian duct syndrome. In other words, a mutation that interrupts Gbb38 production in flies, is analogous to the mutations associated with developmental disorders in different tissues in people.
The genetic analysis doesn't prove that mutations that hinder the production of an analogous signaling protein in humans would be the cause of those diseases, Wharton said. In fact, a longer-form BMP like Gbb38 has yet to be discovered in people. But the new discovery at least suggests the need for research to investigate that link, perhaps first in mice, she said.
Another potential benefit of the finding, she said, is that finding a Gbb38 analogue in humans could improve the current use of BMPs as therapeutics for bone repair, spinal fusions, and reconstruction of maxillofacial bone defects.
"If large forms of human BMPs are indeed present, which is suggested by the three human mutations, then they could be a very useful alternatives to the short BMPs because the large forms are more active in terms of signaling and have different properties in vivo," Wharton said.
Discovery on the wing
In the new paper, aided by an antibody provided by second author Guillermo Marques of the University of Alabama, Akiyama and Wharton were able to discover Gbb38 because they first asked what happened when they interrupted the creation of Gbb15. When they did that, by mutating the genetic instructions that tell enzymes where to cut Gbb15 out of a longer protein, they noticed that signaling activity was only mildly re
|Contact: David Orenstein|