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Delayed dopaminergic neuron differentiation in Lrp6 mutant mice
Author(s) -
CasteloBranco Gonçalo,
Andersson Emma R.,
Minina Eleonora,
Sousa Kyle M.,
Ribeiro Diogo,
Kokubu Chikara,
Imai Kenji,
Prakash Nilima,
Wurst Wolfgang,
Arenas Ernest
Publication year - 2010
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.22094
Subject(s) - biology , wnt signaling pathway , morphogenesis , microbiology and biotechnology , midbrain , lrp6 , neuron , dopaminergic , mutant , endocrinology , signal transduction , neuroscience , dopamine , genetics , central nervous system , gene
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. © 2009 Wiley‐Liss, Inc.