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Fzd3 and Fzd6 deficiency results in a severe midbrain morphogenesis defect
Author(s) -
Stuebner Sebastian,
FausKessler Theresa,
Fischer Thomas,
Wurst Wolfgang,
Prakash Nilima
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.22127
Subject(s) - midbrain , neural tube , biology , frizzled , morphogenesis , neuroepithelial cell , hindbrain , wnt signaling pathway , microbiology and biotechnology , anatomy , neuroscience , embryo , central nervous system , genetics , signal transduction , neural stem cell , gene , stem cell
Wnt/β‐catenin signaling controls the proper development of the mid‐/hindbrain region (MHR) and of midbrain dopaminergic (mDA) neurons, but the Frizzled (Fzd) receptors transducing these signals are still unknown. Fzd3 is expressed throughout the mouse anterior neural tube, whereas Fzd6 is restricted to the MHR. We show that the MHR is properly established and mDA neurons develop normally in Fzd6 −/− mutants, but the number of mDA neurons is initially reduced and recovers at later stages in Fzd3 −/− embryos. Fzd3 −/− ; Fzd6 −/− double mutants exhibit a severe midbrain morphogenesis defect consisting of collapsed brain ventricles, apparent thickening of the neuroepithelium, focal disruption of the ventricular basal lamina and protrusion of individual cells, and increased proliferation at later stages, despite a normal closure of the anterior neural tube and the rescue of the mDA defect in these embryos. Fzd3 and Fzd6 thus control proper midbrain morphogenesis by a yet unknown mechanism in the mouse. Developmental Dynamics 239:246–260, 2010. © 2009 Wiley‐Liss, Inc.