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Cell Mol Life Sci. 2009 Feb;66(4):565-83. doi: 10.1007/s00018-008-8335-4.

The sine oculis homeobox (SIX) family of transcription factors as regulators of development and disease.

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Department of Biology, Indiana University, Bloomington, 47405, USA.


The sine oculis homeobox (SIX) protein family is a group of evolutionarily conserved transcription factors that are found in diverse organisms that range from flatworms to humans. These factors are expressed within, and play pivotal developmental roles in, cell populations that give rise to the head, retina, ear, nose, brain, kidney, muscle and gonads. Mutations within the fly and mammalian versions of these genes have adverse consequences on the development of these organs/tissues. Several SIX proteins have been shown to directly influence the cell cycle and are present at elevated levels during tumorigenesis and within several cancers. This review aims to highlight aspects of (1) the evolutionary history of the SIX family; (2) the structural differences and similarities amongst the different SIX proteins; (3) the role that these genes play in retinal development; and (4) the influence that these proteins have on cell proliferation and growth.

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