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Castelo-Branco, G, Andersson, ER, Minina, E, Sousa, KM, Ribeiro, D, Kokubu, C, Imai, K, Prakash, N, Wurst, W and Arenas, E (2010) Delayed dopaminergic neuron differentiation in Lrp6 mutant mice. Dev. Dyn. 239:211-21


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.


PubMed Online version:10.1002/dvdy.22094


Animals; Bromodeoxyuridine; Cell Differentiation/genetics; Cell Differentiation/physiology; Dopamine/metabolism; Genotype; Homeodomain Proteins/metabolism; Immunohistochemistry; In Situ Hybridization; Mesencephalon/embryology; Mice; Mice, Knockout; Microscopy, Confocal; Morphogenesis/genetics; Neurons/cytology; Neurons/metabolism; Nuclear Receptor Subfamily 4, Group A, Member 2/metabolism; Transcription Factors/metabolism; Tyrosine 3-Monooxygenase/metabolism