EphAs and ephrin-As are expressed in multiple regions of the developing brain and have been implicated in regulating brain size. Here, we report the identification of a novel mechanism in which reverse signaling through ephrin-As controls neural epithelial cell number in the developing brain. Ectopic expression of EphA8-Fc in transgenic embryos induced apoptosis of neural epithelial cells, which was accompanied by a dramatic decrease in brain size. The number of ephrin-A5-expressing cells was significantly reduced in the brain region where EphA8-Fc was ectopically expressed. Furthermore, in vitro culture of the dissociated neuroepithelial cells revealed that EphA8-Fc enhanced apoptotic cell death of the ephrinA5-expressing cells in a caspase-dependent manner. Thus, our results suggest that reverse signaling through ephrin-As is biochemically linked with caspase-dependent proapoptotic signaling during early brain development.
Keywords: EphA; apoptosis; early brain development; ephrin-A.
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