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Depaepe V; Suarez-Gonzalez N; Dufour A; Passante L; Gorski JA; Jones KR; Ledent C; Vanderhaeghen P
Ephrin signalling controls brain size by regulating apoptosis of neural progenitors.
  • Expression literature records: 13
  • Functional annotations (GO): 3
  • Genome features: 14
  • Phenotypic alleles: 2
  • Sequences: 1
Nature
2005
435 (7046) 1244-50
5.592295
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.

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