Researchers at the University of California, San Diego (UCSD) School of Medicine have identified a genetic regulator of brain development that sheds new light on how immature neural cells choose between proliferation and differentiation. Defects in regulating this choice result in brain malformations. Their research will be published on line the week of December 4, in advance of publication in the Proceedings of the National Academy of Sciences (PNAS.)
Bruce Hamilton, Ph.D., associate professor in the Department Medicine, and his colleagues have identified a genetic regulatory pathway that controls a neural precursor cell's decision to self-renew as a dividing precursor or differentiate into a non-dividing neuron. Cells that are unable to differentiate appropriately and continue to proliferate may give rise to brain cancers. On the other hand, cells that differentiate too soon or make too few cells can result in malformations of critical brain structures.
"Development of the brain requires intricate coordination to control the proliferation, differentiation, and connections among different groups of cells," said Hamilton. "We have found a gene in mice, mutated in one kind of malformation, which appears both to promote proliferation and to help coordinate differentiation of immature precursor cells."
The work in Hamilton's lab, led by UCSD Biomedical Sciences graduate students Wendy Alcaraz and David Gold, discovered a specific transcription factor called Zfp423. When Zfp423 is mutated in mice, developmental defects in the cerebellum occur that resemble Dandy-Walker malformations seen in human patients.
Dandy-Walker malformations occur in about one in 25,000 human births. Patients have a congenital malformation in the cerebellum, an area of the brain that controls movement, which can significantly slow motor development and cause progressive enlargement of the skull. Dandy-Walker malformation is frequently associat
Contact: Debra Kain
University of California - San Diego