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The Journal of Neuroscience, July 23, 2003, 23(16):6399-6403

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Identification of a Pax6-Dependent Epidermal Growth Factor Family Signaling Source at the Lateral Edge of the Embryonic Cerebral Cortex

Stavroula Assimacopoulos, Elizabeth A. Grove, and Clifton W. Ragsdale

Department of Neurobiology, Pharmacology, and Physiology, The University of Chicago, Chicago, Illinois 60637

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, Tgf{alpha}, 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 the Small eye (Pax6) mutation and suggest the loss of EGF signaling at least partially explains defects in cortical patterning and cell migration in Small eye mice.

Key words: cortical patterning; Tgf{alpha}; Neuregulin; Sfrp2; Fgf7; Small eye; Pax6; Emx2


Received Dec. 12, 2002; revised May. 7, 2003; accepted May. 16, 2003.




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