Nucleosome regulator Xhmgb3 is required for cell proliferation of the eye and brain as a downstream target of Xenopus rax/Rx1

Rax/Rx is a paired-type homeodomain-containing transcription factor that is essential for cell proliferation in the developing eye and brain. The molecular mechanisms that regulate cell proliferation by rax, however, are largely unknown. Here, we identify the high mobility group B3 gene (hmgb3) as a downstream target of Xenopus rax (Xrax/XRx1). Overexpression of Xhmgb3 results in an increase in eye and brain sizes due to promoted cell proliferation, while morpholino-oligo-mediated knock down of Xhmgb3 reduces eye and brain sizes. In addition, ChIP assays showed that Xhmgb3 is recruited around the promoter region of c-myc to enhance c-myc transcription. We also found that XOptx2 requires rax for its initial expression. Furthermore, we show that Xhmgb3 and XOptx2 are required for retinal development mainly at different developmental stages. Our findings reveal a novel aspect of progenitor cell proliferation during embryonic central nervous system (CNS) development.