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Key gene controlling eye lens development identified

Investigators at St. Jude Children's Research Hospital have discovered in mouse models that a gene called Six3 is one of the earliest critical regulators controlling lens development in the eye of the mammalian embryo.

Mutations in Six3 have been previously identified in patients with holoprosencephaly, a disease that can cause the part of the brain called the cerebrum to fail to divide normally into two lobes. Holoprosencephaly is the most common abnormality of the development of the forebrain (front part of the brain) in humans. A few years ago the St. Jude team demonstrated that Six3 activity is critical for the normal development of the forebrain in mice.

St. Jude researchers have now extended these results by showing in the developing eye that Six3 normally exerts its effect by directly activating Pax6, a gene considered the "master regulator of eye development." In the absence of Six3, Pax6 fails to coordinate the activity of a series of additional genes that cooperate to form the lens. A report on this work appears in the prepublication online issue of The EMBO Journal.

Previously, the researchers were not able to address the gene's possible role in mouse eye formation because inactivation of Six3 significantly disrupted development of the area of the brain where the eye normally forms. The St. Jude team overcame this problem by taking advantage of Cre/loxP-technology, which allowed them to choose the time and place in which to remove Six3 function from specific cells. This permitted the investigators to remove Six3 activity from the presumptive lens ectoderm (PLE)--the area of the developing head where the lens will ultimately form in response to a series of biochemical signals. Following this systematic approach, the St. Jude team demonstrated that Six3 plays its important role in the PLE. The investigators also showed that a key consequence of removing Six3 during early development is that the PLE fails to undergo its normal t
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Source:St. Jude Children's Research Hospital


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