Do Brn’s rule the heart? Brn-3 TFs in cardiac development, defects/disease

Brn-3a (POU4F1) and Brn-3b (POU4F2) transcription factors (TFs) are expressed in developing hearts and increased Brn-3b in Brn-3a KO hearts might partially compensate for loss of Brn-3a but contributes to changes in cardiac morphology that may lead to lethality soon after birth. To analyse possible compensatory effects of these TFs, we attempted to generate double mutant mice lacking both Brn-3a and Brn-3b but early embryonic lethality meant that effects on cardiac development could not be analysed using currently available mouse models. Preliminary studies were undertaken using zebrafish (ZF) because there is high homology between human and ZF Brn-3a (71%) and Brn-3b (87%) and TFs are encoded by single genes in the ZF genome. Studies using morpholinos to target Brn-3a and Brn-3b in ZF embryos showed significant changes in cardiac morphology e.g. failure of heart looping and defective inflow tracts, not seen in single morphants. These results confirm that Brn-3a and Brn-3b are important for normal cardiac development and may partially compensate for each other