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Castelo-Branco, G.* ; Andersson, E.R.* ; Minina, E. ; Sousa, K.M.* ; Ribeiro, D.* ; Kokubu, C.* ; Imai, K. ; Prakash, N. ; Wurst, W. ; Arenas, E.*

Delayed dopaminergic neuron differentiation in Lrp6 mutant mice.

Dev. Dyn. 239, 211-221 (2010)

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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.

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