Rabbit Anti-Human SOX8 (a.a. 298-446) Polyclonal antibody

Vertebrates have evolved electrosensory receptors that detect electrical stimuli on the surface of the skin and transmit them somatotopically to the brain. In chondrichthyans, the electrosensory system is composed of a cephalic network of ampullary organs, known as the ampullae of Lorenzini, that can detect extremely weak electric fields during hunting and navigation. Each ampullary organ consists of a gel-filled epidermal pit containing sensory hair cells, and synaptic connections with primary afferent neurons at the base of the pit that facilitate detection of voltage gradients over large regions of the body. The developmental origin of electroreceptors and the mechanisms that determine their spatial arrangement in the vertebrate head are not well understood. We have analyzed electroreceptor development in the lesser spotted catshark (Scyliorhinus canicula) and show that Sox8 and HNK1, two markers of the neural crest lineage, selectively mark sensory cells in ampullary organs. This represents the first evidence that the neural crest gives rise to electrosensory cells. We also show that pathfinding by cephalic mechanosensory and electrosensory axons follows the expression pattern of EphA4, a well-known guidance cue for axons and neural crest cells in osteichthyans. Expression of EphrinB2, which encodes a ligand for EphA4, marks the positions at which ampullary placodes are initiated in the epidermis, and EphA4 is expressed in surrounding mesenchyme. These results suggest that Eph-Ephrin signaling may establish an early molecular map for neural crest migration, axon guidance and placodal morphogenesis during development of the shark electrosensory system.

BEST1 is highly and preferentially expressed in the retinal pigment epithelium (RPE) and causes Best macular dystrophy when mutated. We previously demonstrated that the human BEST1 upstream region -154 to +38 bp is sufficient to direct expression in the RPE of transgenic mice, and microphthalmia-associated transcription factor (MITF) and OTX2 regulate this BEST1 promoter. However, a number of questions remained. Here, we show that yeast one-hybrid screen with bait corresponding to BEST1 -120 to -88 bp identified the SOX-E factors, SOX8, SOX9, and SOX10. A paired SOX site was found in this bait, and mutation of either of the paired sites significantly decreased BEST1 promoter activity in RPE primary cultures. Among the SOX-E genes, SOX9 is highly and preferentially expressed in the RPE, and chromatin immunoprecipitation with fresh RPE cells revealed binding of SOX9, but not SOX10, to the BEST1 region where the paired SOX site is located. BEST1 promoter activity was increased by SOX9 overexpression and decreased by siRNA-mediated SOX9 knockdown. Importantly, SOX9 physically interacted with MITF and OTX2 and orchestrated synergistic activation of the BEST1 promoter with the paired SOX site playing essential roles. A combination of the expression patterns of SOX9, MITF, and OTX2 yielded tissue distribution remarkably similar to that of BEST1. Lastly, the BEST1 promoter was also active in Sertoli cells of the testis in transgenic mice where SOX9 is highly expressed. These results define SOX9 as a key regulator of BEST1 expression and demonstrate for the first time its functional role in the RPE.