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Dev Dyn. 2010 Jan;239(1):211-21. doi: 10.1002/dvdy.22094.

Delayed dopaminergic neuron differentiation in Lrp6 mutant mice.

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  • 1Laboratory of Molecular Neurobiology, Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.


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.

(c) 2009 Wiley-Liss, Inc.

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