Study in Oct. 1 'Development' shows when, where Alzheimer's, some cancers and genetic ills begin
TALLAHASSEE, Fla. - Biologists at Florida State University have uncovered the pivotal role of a gene called "Cut" that acts as a sort of middleman in cell-to-cell communication.
A DNA-binding protein, Cut interprets and transcribes the developmental signals sent through the "Notch" gene, which regulates a layer of epithelial cells as they replicate and divide. But when Cut garbles those signals the result is uncontrolled cell proliferation, sometimes with dire genetic and health consequences.
Results of the study are described in the Oct. 1 edition of the journal Development.
Led by FSU assistant professor Wu-Min Deng, the research has provided a more precise understanding of just how and where molecular mechanisms that drive cell cycle behavior and fate go wrong along the critical Notch pathway –– a communication channel already associated with the genesis of several genetic and neuromuscular diseases; the most common complex congenital heart disorder; and later life ills such as Alzheimer's, breast and lung cancer, and leukemia.
"We now know that the transcription factor Cut is the key there," said Deng.
Assisted by FSU graduate student and co-author Jianjun Sun, Deng conducted the study using the powerful Drosophila (fruit fly) genetic model. Over the course of a year, they tracked the cell-to-cell communication in Drosophila egg chambers that control cell proliferation.
"We believe the specific cell-to-cell signaling and dysfunction observed in fruit flies is applicable to mammals, which also possess genes Notch and Cut," said Deng.
The researchers traced the journey of transmissions originating from Notch –– which carries information gleaned from other cells –– following the signals down the Notch pathway as Cut linked them to the control of cell proliferation in the egg chambers, which they observed at different stages.
When Cut accurately transcribed the Notch signals, the cells progressed appropriately from the conventional mitosis (replication and division) to the specialized endocycle, where cells cease division but still replicate their DNA.
But if Notch-to-Cut communication and Cut transcription were dysfunctional, so, too, was the cell cycle. In that case, the essential switch from mitosis to the endocycle failed, resulting in unregulated growth.
According to Deng, knowing exactly how and where in the Notch pathway early developmental signals get crossed may be crucial to future fixes, since mutations to the molecular mechanisms there are linked in humans to specific congenital and later life disorders.
"With further study, these findings may aid the development of interventions that target certain diseases precisely where and when they begin at the molecular level," he said.
Deng's focus on Cut since joining the biological sciences faculty at FSU in 2004 followed a Notch study he also co-authored, which appeared in a 2001 issue of Development.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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