FSU Biologists Describe Key Role Of Signal-transcribing Gene In Alzheimer's, Other Ills

A DNA-binding protein, Cut interprets and transcribes thedevelopmental signals sent through the "Notch" gene, which regulates alayer of epithelial cells as they replicate and divide. But when Cutgarbles 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 hasprovided a more precise understanding of just how and where molecularmechanisms that drive cell cycle behavior and fate go wrong along thecritical Notch pathway -- a communication channel already associatedwith the genesis of several genetic and neuromuscular diseases; themost common complex congenital heart disorder; and later life ills suchas 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, Dengconducted the study using the powerful Drosophila (fruit fly) geneticmodel. Over the course of a year, they tracked the cell-to-cellcommunication in Drosophila egg chambers that control cellproliferation.

"We believe the specific cell-to-cell signaling and dysfunctionobserved in fruit flies is applicable to mammals, which also possessgenes Notch and Cut," said Deng.

The researchers traced the journey of transmissions originatingfrom Notch -- which carries information gleaned from other cells --following the signals down the Notch pathway as Cut linked them to thecontrol of cell proliferation in the egg chambers, which they observedat different stages.

When Cut accurately transcribed the Notch signals, the cellsprogressed appropriately from the conventional mitosis (replication anddivision) to the specialized endocycle, where cells cease division butstill replicate their DNA.

But if Notch-to-Cut communication and Cut transcription weredysfunctional, so, too, was the cell cycle. In that case, the essentialswitch from mitosis to the endocycle failed, resulting in unregulatedgrowth.

According to Deng, knowing exactly how and where in the Notchpathway early developmental signals get crossed may be crucial tofuture fixes, since mutations to the molecular mechanisms there arelinked in humans to specific congenital and later life disorders.

"With further study, these findings may aid the development ofinterventions that target certain diseases precisely where and whenthey begin at the molecular level," he said.

Deng's focus on Cut since joining the biological sciencesfaculty at FSU in 2004 followed a Notch study he also co-authored,which appeared in a 2001 issue of Development.

The FSU research was funded in part by the American Heart Association.

Go to http://dev.biologists.org/content/vol132/issue19/ for online access to the Oct. 1 Development and a PDF of the Deng-Sun article "Cut to the endocycle."