That vital step is orchestrated by the product of a single gene called Six3, which guides the formation of the embryonic part of the brain called the forebrain. The forebrain is destined to contain, among other structures, the eyes, olfactory center and cerebrum.
St. Jude scientists showed that the Six3 gene ensures proper development of the forebrain by halting the activity of another gene, called Wnt1, which had previously been shown to control the development of more posterior parts of the brain.
The action of the Six3 protein in directly blocking the activity of the Wnt1 protein prevents abnormal extension of the posterior part of the embryonic brain into what is normally destined to be the forebrain. Once protected by Six3, the forebrain matures, giving rise to some of the higher centers that control a variety of critical functions such as thought, memory and the senses of sight and smell.
We showed that Six3 is one of the key elements preventing Wnt1 from disrupting normal development of the forebrain, said Oleg V. Lagutin, PhD, a post-doctoral fellow in the Department of Genetics at St. Jude. Lagutin, who works in the laboratory of Guillermo Oliver, Ph.D., an associate member in the department, is the lead author of a report on this work, which appears in the Feb. 1, 2003 issue of the journal Genes & Development.
The St. Jude researchers showed that in mutant mice lacking both copies of the gene for Six3 (Six3-/- mice), there was abnormal extension of the posterior brain into the anterior area of the brain, i.e., the part that would normally have developed into the forebrain. This malformation was caused by the abnormal expansion of Wnt1 a
Contact: Bonnie Cameron
St. Jude Children's Research Hospital