| First Author | Depaepe V | Year | 2005 |
| Journal | Nature | Volume | 435 |
| Issue | 7046 | Pages | 1244-50 |
| PubMed ID | 15902206 | Mgi Jnum | J:99355 |
| Mgi Id | MGI:3582020 | Doi | 10.1038/nature03651 |
| Citation | Depaepe V, et al. (2005) Ephrin signalling controls brain size by regulating apoptosis of neural progenitors. Nature 435(7046):1244-50 |
| abstractText | Mechanisms controlling brain size include the regulation of neural progenitor cell proliferation, differentiation, survival and migration. Here we show that ephrin-A/EphA receptor signalling plays a key role in controlling the size of the mouse cerebral cortex by regulating cortical progenitor cell apoptosis. In vivo gain of EphA receptor function, achieved through ectopic expression of ephrin-A5 in early cortical progenitors expressing EphA7, caused a transient wave of neural progenitor cell apoptosis, resulting in premature depletion of progenitors and a subsequent dramatic decrease in cortical size. In vitro treatment with soluble ephrin-A ligands similarly induced the rapid death of cultured dissociated cortical progenitors in a caspase-3-dependent manner, thereby confirming a direct effect of ephrin/Eph signalling on apoptotic cascades. Conversely, in vivo loss of EphA function, achieved through EphA7 gene disruption, caused a reduction in apoptosis occurring normally in forebrain neural progenitors, resulting in an increase in cortical size and, in extreme cases, exencephalic forebrain overgrowth. Together, these results identify ephrin/Eph signalling as a physiological trigger for apoptosis that can alter brain size and shape by regulating the number of neural progenitors. |
