SIX3 : SIX homeobox 3

Description

The SIX3 (SIX homeobox 3) is a protein-coding gene located on chromosome 2.

The SIX3 gene provides instructions for making a protein that plays an important role in the development of the eyes and front part of the brain (forebrain). This protein is a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity of certain genes. The SIX3 protein regulates genes involved in several signaling pathways that are important for embryonic development. Some of these genes are turned on (activated) by the SIX3 protein and others are turned off (repressed).One gene that is activated by the SIX3 protein is the SHH gene, which provides instructions for making a protein called Sonic Hedgehog. Among its many functions, Sonic Hedgehog helps establish the right and left halves (hemispheres) of the forebrain. The SIX3 protein also regulates genes involved in the formation of the lens of the eye and the specialized tissue at the back of the eye that detects light and color (the retina).

SIX3 is a transcription factor that can act as both a repressor and activator of gene expression by binding to a specific DNA sequence called the ATTA homeodomain. It plays a crucial role in the development of the forebrain, eyes, and pituitary gland. In the forebrain, SIX3 represses the expression of WNT1, allowing for the formation of a structure called the zona limitans intrathalamica (ZLI), which is essential for the proper development of the diencephalon. SIX3 also directly activates the expression of SHH in the ventral midline of the rostral diencephalon, which in turn maintains SIX3 expression. SIX3 is also required for the formation of the telencephalon. During postnatal brain development, SIX3 promotes the maturation of radial glia into ependymal cells by regulating neuroblast proliferation and migration. In the eye, SIX3 activates the expression of PAX6, which in turn activates SIX3, leading to the expression of PDGFRA and CCND1, promoting cell proliferation during lens development. SIX3 also directly represses the expression of WNT8B in the anterior neural plate, which is essential for neuroretina development. SIX3's actions during retina and lens development are dependent on the proteins TLE5 and TLE4. SIX3 also regulates the expression of various genes during eye development, such as repressing the CRYGF promoter and activating RHO transcription. It also contributes to the formation of the optic cup and promotes the formation of optic vesicle-like structures. In the pituitary gland, SIX3 acts in parallel or alternatively with HESX1 to control cell proliferation through the Wnt/beta-catenin pathway. Finally, SIX3 plays a role in eye development by suppressing WNT1 expression and in dorsal-ventral patterning by repressing BMP signaling.

SIX3 is also known as HPE2.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing