Linked Life Data

19607821

Source:http://linkedlifedata.com/resource/pubmed/id/19607821

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-8-31
pubmed:abstractText
Mesodiencephalic dopaminergic neurons control voluntary movement and reward based behaviours. Their dysfunction can lead to neurological disorders, including Parkinson's disease. These neurons are thought to arise from progenitors in the floor plate of the caudal diencephalon and midbrain. Members of the Foxa family of forkhead/winged helix transcription factor, Foxa1 and Foxa2, have previously been shown to regulate neuronal specification and differentiation of mesodiencephalic progenitors. However, Foxa1 and Foxa2 are also expressed earlier during regional specification of the rostral brain. In this paper, we have examined the early function of Foxa1 and Foxa2 using conditional mutant mice. Our studies show that Foxa1 and Foxa2 positively regulate Lmx1a and Lmx1b expression and inhibit Nkx2.2 expression in mesodiencephalic dopaminergic progenitors. Subsequently, Foxa1 and Foxa2 function cooperatively with Lmx1a and Lmx1b to regulate differentiation of mesodiencephalic dopaminergic neurons. Chromatin immunoprecipitation experiments indicate that Nkx2.2 and TH genes are likely direct targets of Foxa1 and Foxa2 in mesodiencephalic dopaminergic cells in vivo. Foxa1 and Foxa2 also inhibit GABAergic neuron differentiation by repressing the Helt gene in the ventral midbrain. Our data therefore provide new insights into the specification and differentiation of mesodiencephalic dopaminergic neurons and identifies Foxa1 and Foxa2 as essential regulators in these processes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1095-564X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
333
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
386-96
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Foxa1 and Foxa2 function both upstream of and cooperatively with Lmx1a and Lmx1b in a feedforward loop promoting mesodiencephalic dopaminergic neuron development.
pubmed:affiliation
Division of Developmental Neurobiology, MRC National Institute for Medical Research, The Ridgeway, London, NW7 1AA, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't