Macrophage migration inhibitory factor inhibits BMP-4 induced apoptosis

Non-canonical bone morphogenic protein (BMP) pathway signaling plays a critical role during embryonic neurogenesis, inducing apoptosis and eliminating an excess of neural progenitor cells, in preparation for the population of the neural stem cell niches. Our previous work discovered that non-canonical BMP signaling also induced the expression of the anti-apoptotic cytokine macrophage migration inhibitory factor (MIF). Because there are residual neural progenitors that escape BMP induced apoptosis, we believed the expression of MIF could be used to counter this specific type of developmental apoptosis. In vitro studies using P19 cells and ex vivo studies using E13 neural progenitor from wild type and mif-/-mice revealed that overexpression of mif was able to counteract BMP induced apoptosis, while in contrast ablation of mif resulted in a dramatic increase in apoptosis. Despite this finding, it is interesting to note that mif-/-mice, while presenting an overall increase in apoptosis are viable, ablation of mif expression in zebrafish and frog are embryonic lethal, suggesting a redundant or non-critical role of MIF in the developing mammalian embryo.