Linked Life Data

12668639

Source:http://linkedlifedata.com/resource/pubmed/id/12668639

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2003-4-1
pubmed:abstractText
Leptomeningeal glioneuronal heterotopias are a focal type of cortical dysplasia in which neural cells migrate aberrantly into superficial layers of the cerebral cortex and meninges. These heterotopias are frequently observed as microscopic abnormalities in the brains of individuals with central nervous system (CNS) malformations and epilepsy. Previous work has demonstrated that the function of Emx2, which encodes a homeodomain transcription factor, is essential for development of the cortical preplate, which gives rise to the marginal zone and subplate. However, transcriptional targets of EMX2 during CNS development are unknown. We report that leptomeningeal glioneuronal heterotopias form in Emx2(-/-) mice that are equivalent to human lesions. Additionally, we observed ectopic expression of Wnt1 in the embryonic roofplate organizer region and dorsal telencephalon. To determine the phenotypic consequences of such Wnt1 misexpression, we deleted a putative EMX2 DNA-binding site from the Wnt1 enhancer and used this to misexpress Wnt1 in the developing murine CNS. Heterotopias were detected in transgenic mice as early as 13.5 days postcoitum, consistent with a defect of preplate development during early phases of radial neuronal migration. Furthermore, we observed diffuse abnormalities of reelin- and calretinin-positive cell populations in the marginal zone and subplate similar to those observed in Emx2-null animals. Taken together, these findings indicate that EMX2 is a direct repressor of Wnt1 expression in the developing mammalian telencephalon. They further suggest that EMX2-Wnt1 interactions are essential for normal development of preplate derivatives in the mammalian cerebral cortex.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0950-1991
pubmed:author
pubmed:issnType
Print
pubmed:volume
130
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2275-87
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12668639-Animals, pubmed-meshheading:12668639-Binding Sites, pubmed-meshheading:12668639-Choristoma, pubmed-meshheading:12668639-Embryo, Mammalian, pubmed-meshheading:12668639-Enhancer Elements, Genetic, pubmed-meshheading:12668639-Gene Expression Regulation, Developmental, pubmed-meshheading:12668639-Homeodomain Proteins, pubmed-meshheading:12668639-Humans, pubmed-meshheading:12668639-In Situ Hybridization, pubmed-meshheading:12668639-Meninges, pubmed-meshheading:12668639-Mice, pubmed-meshheading:12668639-Mice, Transgenic, pubmed-meshheading:12668639-Neuroglia, pubmed-meshheading:12668639-Neurons, pubmed-meshheading:12668639-Proto-Oncogene Proteins, pubmed-meshheading:12668639-Telencephalon, pubmed-meshheading:12668639-Transcription Factors, pubmed-meshheading:12668639-Transgenes, pubmed-meshheading:12668639-Wnt Proteins, pubmed-meshheading:12668639-Wnt1 Protein, pubmed-meshheading:12668639-Zebrafish Proteins
pubmed:year
2003
pubmed:articleTitle
Loss of Emx2 function leads to ectopic expression of Wnt1 in the developing telencephalon and cortical dysplasia.
pubmed:affiliation
Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 0215, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't