Identification of aPax6-Dependent Epidermal Growth Factor Family Signaling Source at the Lateral Edge of the Embryonic Cerebral Cortex

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Abstract
In an emerging model, area patterning of the mammalian cerebral cortex is regulated in part by embryonic signaling centers. Two have been identified: an anterior telencephalic source of fibroblast growth factors and the cortical hem, a medial structure expressing winglessint (WNT) and bone morphogenetic proteins. We describe a third signaling source, positioned as a mirror image of the cortical hem, along the lateral margin of the cortical primordium. The cortical antihem is identified by gene expression for three epidermal growth factor (EGF) family members, Tgfα, Neuregulin 1, and Neuregulin 3, as well as two other signaling molecules, Fgf7 and the secreted WNT antagonist Sfrp2. We find that the antihem is lost in mice homozygous for theSmall eye(Pax6) mutation and suggest the loss of EGF signaling at least partially explains defects in cortical patterning and cell migration inSmall eyemice.