Principal investigator: Peter Carlsson |
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PhD Students: Åsa Blixt, Mattias Ormestad, Jeanette Astorga
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Description of projects |
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Forkhead genes encode transcription factors with a conserved "winged helix"
DNA binding domain and play essential roles in a number of developmental
processes. We study the function of mammalian forkhead genes using mouse
models and explore their contribution to human genetic disorders.
The forkhead gene FoxE3 is essential for normal development of the lens. Studies of proliferation, apoptosis and expression of cell cycle proteins and differentiation markers in FoxE3 null mice indicate that growth and survival of the anterior lens epithelium, as well as inhibition of premature lens fiber differentiation, depend on functional FoxE3. Mice heterozygous for FoxE3 mutations develop a less severe version of the phenotype with central leucoma, keratolenticular adhesion and sometimes polar cataract. This corresponds to a condition known as Peters' anomaly in humans and we have found that some patients diagnosed with this disease have mutations in FoxE3. FoxF1 is expressed in mesoderm of the primitive streak, lateral plate and extraembryonic structures during early embryonic development. Later, the expression is found mostly in splanchnic mesenchyme and in extraembryonic blood vessels. Homozygous FoxF1 knockout embryos die at midgestation due to lack of placentation and extraembryonic vascularization. Heterozygotes have an elevated perinatal mortality due to lung and foregut malformations. In these tissues FoxF1 is activated by Sonic hedgehog and in vitro organ culture experiments show that FoxF1 is an important mediator of hedgehog signaling. Our current research interests include analysis of the function of Fox proteins as mediators of hedgehog signaling; mesoderm differentiation; eye development; and gene dosage effects as a mechanism behind human genetic disorders. |
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Publications |
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Department of Molecular Biology
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