Identification of a Pax6-dependent epidermal growth factor family signaling source at the lateral edge of the embryonic cerebral cortex.
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.
Assimacopoulos
Stavroula
S
Department of Neurobiology, Pharmacology, and Physiology, The University of Chicago, Chicago, Illinois 60637, USA.
Grove
Elizabeth A
EA
Ragsdale
Clifton W
CW
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D002540:Cerebral Cortex / Q000196:embryology* / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000235:genetics*; D005124:Eye Abnormalities / Q000196:embryology* / Q000235:genetics; D005136:Eye Proteins; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006720:Homozygote; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D009024:Morphogenesis; D005810:Multigene Family; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism; D020880:Neuregulins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D012097:Repressor Proteins; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D000099260:Empty Spiracles Homeobox Proteins; D000094742:Secreted Frizzled-Related Proteins
D002352:Carrier Proteins; D004815:Epidermal Growth Factor; D005136:Eye Proteins; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D020890:Neuregulin-1; D020880:Neuregulins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D011506:Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D016211:Transforming Growth Factor alpha; D000099260:Empty Spiracles Homeobox Proteins; C496454:Fgf7 protein, mouse; C486357:NRG3 protein, human; C108113:Nrg3 protein, mouse; C000605730:PAX6 protein, human; C000605732:Pax6 protein, mouse; C491628:Sfrp2 protein, mouse; D000094742:Secreted Frizzled-Related Proteins