Journal
DEVELOPMENTAL DYNAMICS
Volume 239, Issue 1, Pages 211-221Publisher
WILEY
DOI: 10.1002/dvdy.22094
Keywords
Lrp; Wnt; dopaminergic; neurogenesis, precursor; midbrain
Categories
Funding
- Swedish Research Council [VR2008, 2811, DBRM]
- Swedish Foundation for Strategic Research
- Norwegian Research Council
- Karolinska Institutet
- Michael J Fox Foundation,
- European Union [FP7-Health-2007-B-222999, LSHG-CT-2006-037445]
- BMBF National Genome Research [FKZ 01GS08174]
- Virtual Institute on Neurodegeneration and Ageing [VH-VI-252]
- Initiative and Networking Fund [HA-215]
- Bayerischer Forschungsverbund 'ForNeuroCell' [F2-F2410-10c/20697]
- Deutsche Forschungsgemeinschaft (DFG) [SFB 596, WU 164/3-2, WU 164/4-1]
- European Commission
- Portuguese Fundacao para a Ciencia e Tecnologia
- Calouste Gulbenkian Foundation
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Wnts 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. Developmental Dynamics 239:211-221, 2010. (C) 2009 Wiley-Liss, Inc.
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