Anti-Six3 Antibody Picoband® Fluoro550 Conjugated

Homeobox protein SIX3 is a protein that in humans is encoded by the SIX3 gene. This gene encodes a member of the sine oculishomeobox transcription factor family. The encoded protein plays a role in eye development. Mutations in SIX3 are the cause of a severe brain malformation, called holoprosencephaly type 2 (HPE2) . In HPE2, the brain fails to separate into two hemispheres during early embryonic development, leading to eye and brain malformations, which result in serious facial abnormalities. A mutant zebrafish knockout model has been developed, in which the anterior part of the head was missing due to the atypical increase of Wnt1 activity. When injected with SIX3, these zebrafish embryos were able to successfully develop a normal forebrain. When SIX3 was turned off in mice, resulting in a lack of retina formation due to excessive expression of Wnt8b in the region where the forebrain normally develops. Both of these studies demonstrate the importance of SIX3 activity in brain and eye development.

Highly expressed in placenta, lung, kidney, testis and ovary. Weakly expressed in spleen and thymus. Not expressed in peripheral blood lymphocytes. Detected in hippocampus.

Transcriptional regulator which can act as both a transcriptional repressor and activator by binding a ATTA homeodomain core recognition sequence on these target genes. During forebrain development represses WNT1 expression allowing zona limitans intrathalamica formation and thereby ensuring proper anterio-posterior patterning of the diencephalon and formation of the rostral diencephalon. Acts as a upstream activator of SHH expression in the rostral diencephalon ventral midline and that in turn SHH maintains its expression. In addition, Six3 activity is required for the formation of the telencephalon. During postnatal stages of brain development is necessary for ependymal cell maturation by promoting the maturation of radial glia into ependymal cells through regulation of neuroblast proliferation and migration. Acts on the proliferation and differentiation of neural progenitor cells through activating transcription of CCND1 AND CCND2. During early lens formation plays a role in lens induction and specification by activating ly PAX6 in the presumptive lens ectoderm. In turn PAX6 activates SIX3 resulting in activation of PDGFRA and CCND1 promoting cell proliferation. Also is required for the neuroretina development by ly suppressing WNT8B expression in the anterior neural plate territory. Its action during retina development and lens morphogenesis is AES and TLE4-dependent manner. Furthermore, during eye development regulates several genes expression. Before and during early lens development represses the CRYGF promoter by binding a SIX repressor element. ly activates RHO transcription, or cooperates with CRX or NRL. Six3 functions also in the formation of the proximodistal axis of the optic cup, and promotes the formation of optic vesicles-like structures. During pituitary development, acts in parallel or alternatively with HESX1 to control cell proliferation through Wnt/beta-catenin pathway (By similarity) . Plays a role in eye development by suppressing WNT1 expression and in dorsal- ventral patterning by repressing BMP signaling pathway. .

1. Lagutin OV, Zhu CC, Kobayashi D, Topczewski J, Shimamura K, Puelles L, Russell HR, McKinnon PJ, Solnica-Krezel L, Oliver G (Feb 2003) . Six3 repression of Wnt signaling in the anterior neuroectoderm is essential for vertebrate forebrain development. Genes & Development. 17 (3) : 368–79. 2. Lavado A, Lagutin OV, Oliver G (Feb 2008) . Six3 inactivation causes progressive caudalization and aberrant patterning of the mammalian diencephalon. Development. 135 (3) : 441–50. 3. Liu W, Lagutin O, Swindell E, Jamrich M, Oliver G (Oct 2010) . Neuroretina specification in mouse embryos requires Six3-mediated suppression of Wnt8b in the anterior neural plate. The Journal of Clinical Investigation. 120 (10) : 3568–77. 4. Wallis DE, Roessler E, Hehr U, Nanni L, Wiltshire T, Richieri-Costa A, Gillessen-Kaesbach G, Zackai EH, Rommens J, Muenke M (Jun 1999) . Mutations in the homeodomain of the human SIX3 gene cause holoprosencephaly. Nature Genetics. 22 (2) : 196–8.