Abstract

Brd2, Bromodomain-containing-2, is a transcriptional co-regulator implicated in apoptosis and mitosis in mammals, and in homeotic gene regulation during development in Drosophila. Disruption of Brd2 expression in humans may confer susceptibility to Juvenile Myoclonic Epilepsy, presumably by contributing to abnormal brain morphogenesis. Brd2-knockdown zebrafish embryos, in which expression is reduced by morpholino oligomers, exhibit characteristic brain abnormalities at 24-hours post-fertilization (hpf). As brain development depends largely on a proper balance of apoptosis and proliferation, the misregulation of programmed cell death may be a mechanism by which Brd2-knockdown brain abnormalities arise. At 24hpf, we found a significant increase in apoptosis throughout the brain where morphological abnormalities are observed. At 10hpf, PCD in the morphant embryo significantly decreased, suggesting a bimodal, context-dependent function of Brd2. This study is the first quantify apoptosis in the Brd2-knockdown embryo to explore the mechanism by which abnormal brain development occurs via misexpression of Brd2.