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pubmed-article:19795519pubmed:abstractTextWnts are known to bind and activate multiple membrane receptors/coreceptors and to regulate dopaminergic (DA) neuron development and ventral midbrain (VM) morphogenesis. The low density lipoprotein receptor-related protein (Lrp6) is a Wnt co-receptor, yet it remains unclear whether Lrp6 is required for DA neuron development or VM morphogenesis. Lrp6 is expressed ubiquitously in the developing VM. In this study, we show that Lrp6(-/-) mice exhibit normal patterning, proliferation and cell death in the VM, but display a delay in the onset of DA precursor differentiation. A transient 50% reduction in tyrosine hydroxylase-positive DA neurons and in the expression of DA markers such as Nurr1 and Pitx3, as well as a defect in midbrain morphogenesis was detected in the mutant embryos at embryonic day 11.5. Our results, therefore, suggest a role for Lrp6 in the onset of DA neuron development in the VM as well as a role in midbrain morphogenesis.lld:pubmed
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pubmed-article:19795519pubmed:copyrightInfo(c) 2009 Wiley-Liss, Inc.lld:pubmed
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pubmed-article:19795519pubmed:volume239lld:pubmed
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pubmed-article:19795519pubmed:articleTitleDelayed dopaminergic neuron differentiation in Lrp6 mutant mice.lld:pubmed
pubmed-article:19795519pubmed:affiliationLaboratory of Molecular Neurobiology, Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.lld:pubmed
pubmed-article:19795519pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:19795519pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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