Cloning and cortical expression of rat Emx2 and adenovirus-mediated overexpression to assess its regulation of area-specific targeting of thalamocortical axons
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Cloning and cortical expression of rat Emx2 and adenovirus-mediated overexpression to assess its regulation of area-specific targeting of thalamocortical axons. / Leingärtner, Axel; Richards, Linda J; Dyck, Richard H; Akazawa, Chihiro; O'Leary, Dennis D M.
In: CEREB CORTEX, Vol. 13, No. 6, 01.06.2003, p. 648-60.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Cloning and cortical expression of rat Emx2 and adenovirus-mediated overexpression to assess its regulation of area-specific targeting of thalamocortical axons
AU - Leingärtner, Axel
AU - Richards, Linda J
AU - Dyck, Richard H
AU - Akazawa, Chihiro
AU - O'Leary, Dennis D M
PY - 2003/6/1
Y1 - 2003/6/1
N2 - A goal of this study was to use recombinant adenovirus (AdV) to ectopically express Emx2 in the embryonic neocortex as a gain-of-function approach to study its role in the area-specific targeting of thalamocortical axons (TCAs), using the rat as a model. First, we cloned the cDNA for the full-length coding region of rat Emx2, a homologue of Drosophila empty spiracles. We also used this sequence to define the full-length coding region of mouse Emx2 from genomic DNA. Our analysis of Emx2 expression shows that in rat, as reported in mouse, Emx2 is expressed in high caudal to low rostral, and high medial to low lateral, gradients across the cortex throughout cortical neurogenesis, and expression is primarily restricted to progenitors in the neuroepithelium. We also carried out an analysis of the distribution of cells infected with a replication defective recombinant type 5 adenovirus (AdV) containing a CAG/LacZ expression construct, following an injection into the lateral ventricle of the cerebral hemisphere at different stages of embryonic cortical neurogenesis. AdV-infected cells are broadly distributed tangentially, but their laminar distribution is differentially restricted and reflects the temporal sequence of generation of cortical neurons. This finding indicates that the AdV predominantly infects progenitors in the ventricular zone, which leads to a preferential labeling of their immediate progeny, and infects cells that have recently become postmitotic and have yet to move far from the ventricular surface. We then show that AdV-mediated ectopic Emx2 expression results in aberrant intracortical pathfinding and areal targeting of TCAs from the dorsal lateral geniculate nucleus. These findings indicate that EMX2 imparts positional information normally associated with caudal cortical areas, such as the primary visual area, that influences the area-specific targeting of TCAs. These results are consistent with a role for EMX2 in areal specification of the neocortex as suggested by recent analyses of Emx2 null mutants.
AB - A goal of this study was to use recombinant adenovirus (AdV) to ectopically express Emx2 in the embryonic neocortex as a gain-of-function approach to study its role in the area-specific targeting of thalamocortical axons (TCAs), using the rat as a model. First, we cloned the cDNA for the full-length coding region of rat Emx2, a homologue of Drosophila empty spiracles. We also used this sequence to define the full-length coding region of mouse Emx2 from genomic DNA. Our analysis of Emx2 expression shows that in rat, as reported in mouse, Emx2 is expressed in high caudal to low rostral, and high medial to low lateral, gradients across the cortex throughout cortical neurogenesis, and expression is primarily restricted to progenitors in the neuroepithelium. We also carried out an analysis of the distribution of cells infected with a replication defective recombinant type 5 adenovirus (AdV) containing a CAG/LacZ expression construct, following an injection into the lateral ventricle of the cerebral hemisphere at different stages of embryonic cortical neurogenesis. AdV-infected cells are broadly distributed tangentially, but their laminar distribution is differentially restricted and reflects the temporal sequence of generation of cortical neurons. This finding indicates that the AdV predominantly infects progenitors in the ventricular zone, which leads to a preferential labeling of their immediate progeny, and infects cells that have recently become postmitotic and have yet to move far from the ventricular surface. We then show that AdV-mediated ectopic Emx2 expression results in aberrant intracortical pathfinding and areal targeting of TCAs from the dorsal lateral geniculate nucleus. These findings indicate that EMX2 imparts positional information normally associated with caudal cortical areas, such as the primary visual area, that influences the area-specific targeting of TCAs. These results are consistent with a role for EMX2 in areal specification of the neocortex as suggested by recent analyses of Emx2 null mutants.
KW - Adenoviridae
KW - Adenoviruses, Human
KW - Amino Acid Sequence
KW - Animals
KW - Animals, Newborn
KW - Axons
KW - Base Sequence
KW - Cell Count
KW - Cerebral Cortex
KW - Cerebral Ventricles
KW - Cloning, Molecular
KW - Female
KW - Gene Expression Regulation, Developmental
KW - Genetic Vectors
KW - Homeodomain Proteins
KW - Molecular Sequence Data
KW - Neocortex
KW - Rats
KW - Recombinant Proteins
KW - Thalamus
KW - Transcription Factors
KW - Transcription, Genetic
M3 - SCORING: Journal article
C2 - 12764041
VL - 13
SP - 648
EP - 660
JO - CEREB CORTEX
JF - CEREB CORTEX
SN - 1047-3211
IS - 6
ER -