EMX2 Regulates Sizes and Positioning of the Primary Sensory and Motor Areas in Neocortex by Direct Specification of Cortical Progenitors
Autor: | Dennis D.M. O'Leary, Tadashi Hamasaki, Axel Leingärtner, Thomas Ringstedt |
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Rok vydání: | 2004 |
Předmět: |
Genetically modified mouse
PAX6 Transcription Factor Neuroscience(all) Transgene EMX2 Thalamus Mice Transgenic Neocortex Biology Mice 03 medical and health sciences 0302 clinical medicine FGF8 medicine Animals Humans Paired Box Transcription Factors Eye Proteins Cell Size 030304 developmental biology Homeodomain Proteins Mice Knockout 0303 health sciences Stem Cells General Neuroscience fungi Motor Cortex Gene Expression Regulation Developmental Somatosensory Cortex Rats Mice Inbred C57BL Repressor Proteins medicine.anatomical_structure Homeobox PAX6 Neuroscience 030217 neurology & neurosurgery Transcription Factors |
Zdroj: | Neuron. 43:359-372 |
ISSN: | 0896-6273 |
DOI: | 10.1016/j.neuron.2004.07.016 |
Popis: | 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. |
Databáze: | OpenAIRE |
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