An international collaboration of scientists, led by Dr. Guillermo Oliver at St. Jude Children's Research Hospital (Memphis, TN) has identified a single gene, called Six3, as a crucial factor in the normal development of the vertebrate forebrain -- the part of the brain that is responsible for smell, memory storage, intelligence, and vision, as well as the regulation of body temperature, breathing, and sleep. Published in the February 1 issue of Genes & Development, this discovery also sheds light on a possible mechanistic basis for the human congenital brain defect, holoprosencephaly.
Holoprosencephaly (HPE) is a brain malformation characterized by the failure of the forebrain to divide into hemispheres during development. While it is estimated that HPE affects 1 in 5,000-10,000 live births, the real incidence may by as high as 1 in 200-250 fetuses, owing to the high rates of spontaneous abortion of those severely affected. Although not the sole culprit, mutations in the Six3 gene can cause HPE.
Dr. Oliver and colleagues are helping to understand why.
"This work adds another player and another step towards deciphering the molecules and mechanisms involved in vertebrate head development in normal and pathological conditions, " explains Dr. Oliver.
The researchers found that in mice, the protein encoded by the Six3 gene (SIX3) secures the identity of anterior (forebrain) neural cells by blocking out a posteriorizing signal that sweeps through the putative forebrain during day 8.0-8.5 of embryogenesis, and determines the identity of more posterior brain structures. This posteriorizing signal is transmitted through the Wnt family of secreted, cell-to-cell signaling proteins.
To examine the role of SIX3 in vivo, Dr. Oliver and colleagues generated transgenic mice deficient in Six3. These Six3-mutant mice died at birth, lacking the rostral forebrain and most anterior head structures, like the eyes and nose. Dr. Oliver and colleaguPage: 1 2 Related biology news :1
Contact: Heather Cosel
Cold Spring Harbor Laboratory
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