EMX2 regulates sizes and positioning of the primary sensory and motor areas in neocortex by direct specification of cortical progenitors.
Genetic studies of neocortical area patterning are limited, because mice deficient for candidate regulatory genes die before areas emerge and have other complicating issues. To define roles for the homeodomain transcription factor EMX2, we engineered nestin-Emx2 transgenic mice that overexpress Emx2 in cortical progenitors coincident with expression of endogenous Emx2 and survive postnatally. Cortical size, lamination, thalamus, and thalamocortical pathfinding are normal in homozygous nestin-Emx2 mice. However, primary sensory and motor areas are disproportionately altered in size and shift rostrolaterally. Heterozygous transgenics have similar but smaller changes. Opposite changes are found in heterozygous Emx2 knockout mice. Fgf8 expression in the commissural plate of nestin-Emx2 mice is indistinguishable from wild-type, but Pax6 expression is downregulated in rostral cortical progenitors, suggesting that EMX2 repression of PAX6 specification of rostral identities contributes to reduced rostral areas. We conclude that EMX2 levels in cortical progenitors disproportionately specify sizes and positions of primary cortical areas.
Molecular Neurobiology Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Tadashi
T
Hamasaki
Axel
A
Leingärtner
Thomas
T
Ringstedt
Dennis D M
DD
O'Leary
D000818:Animals; D048429:Cell Size / Q000235:genetics; D005136:Eye Proteins; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009044:Motor Cortex / Q000196:embryology / Q000378:metabolism*; D019579:Neocortex / Q000196:embryology / Q000378:metabolism*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology; D013003:Somatosensory Cortex / Q000196:embryology / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins
D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins; C000605730:PAX6 protein, human; C000605732:Pax6 protein, mouse; C000605733:Pax6 protein, rat