High impact information on Six4

• Both of these proteins accumulate in the nucleus of C2C12 myogenic cells, and transient transfection experiments confirm that Six1 and Six4 are able to transactivate a reporter gene containing MEF3 sites [1].
• Six4, a putative myogenin gene regulator, is not essential for mouse embryonal development [2].
• Our results indicate that Six4 is not essential for mouse embryogenesis and suggest that other members of the Six family seem to compensate for the loss of Six4 [2].
• Cotransfection assays were performed with various combinations of Six and Eya to assess their effects on a potential natural target, myogenin promoter, and on a synthetic promoter, the thymidine kinase gene promoter fused to multimerized Six4 binding sites [3].
• At the limb bud level, Six1 and Six4 homeogenes control early steps of myogenic cell delamination and migration from the somite through the control of Pax3 gene expression [4].

Biological context of Six4

• In mammals, Six5, Six4 and Six1 genes are co-expressed during mouse myogenesis [4].
• The Six1/Six4-deficient mice exhibited more severe kidney phenotypes than the Six1-deficient mice; kidney and ureter agenesis was observed in all the neonates examined [5].
• The localization of Six4-like immunoreactivity (Six4-LI) showed a temporally regulated pattern: During embryonic development, Six4-LI was found in the nuclei of cells located at the inner neuroblastic layer of the retina as early as on ED12, nearly corresponding to the onset of retinal cell differentiation [6].
• The Six4/AREC3 gene was originally isolated as a regulatory factor which bound to the positive regulatory region of the Na, K-ATPase alpha 1 subunit [6].
• Loss of both Six1 and Six4 in mice caused severe defects in the trigeminal ganglia, wherein massive apoptosis accompanied by activation of caspase-3 was observed at early but not late stages of gangliogenesis [7].

Anatomical context of Six4

• Production of Six2 was detected at E8.5 mainly in the mesenchyme, while Six4 was present in nuclei of neuronal cells in the peripheral region of the mantle layer of developing brain and spinal cord and in various ganglia at E10.5 and E11 [8].
• In contrast, Six4 was detected in a variety of cultured cell lines, including HeLa, 3T3, MDCK and C2C12 [8].
• These results highlight the fact that Six1 and Six4 have collaborative functions in the metanephros but not in the mesonephros [5].
• Expression of Six4 subfamily genes (Six4.1, Six4.2) was present in the developing visceral arches, placodal derivatives (otic vesicle, olfactory system), head mesenchyme and the eye [9].
• Six1 and Six4 promote survival of sensory neurons during early trigeminal gangliogenesis [7].

Other interactions of Six4

• Six1 and Six4 homeoproteins are required for Pax3 and Mrf expression during myogenesis in the mouse embryo [4].
• The distribution of Six2 and Six4 was examined by immunostaining in the developing mouse embryo [8].
• Slc12a2 is a direct target of two closely related homeobox proteins, Six1 and Six4 [10].

Analytical, diagnostic and therapeutic context of Six4

• Sequence analysis indicates that AREC3 has an extensive homology with the Drosophila sine oculis gene product required for development of the entire visual system [Cheyette et al.(1994) Neuron 12, 977-996] [11].
• Immunohistochemistry revealed that AREC3 localized to the nucleus and cytoplasm of myoblast C2C12 cells, and the production of AREC3 is augmented during muscle differentiation [11].

References