TY - JOUR
T1 - Increased Wnt levels in the neural tube impair the function of adherens junctions during neurulation
AU - Shariatmadari, Maria
AU - Peyronnet, Julie
AU - Papachristou, Panagiotis
AU - Horn, Zachi
AU - Sousa, Kyle M.
AU - Arenas, Ernest
AU - Ringstedt, Thomas
N1 - Funding Information:
We wish to thank Prof. Masatoshi Takeichi for kindly providing the N-cadherin riboprobe template. We also thank Prof. Hugo Lagercrantz for his generous support, Dr. Ola Hermanson and Prof. Carlos Ibanéz for valuable comments on the manuscript, and Eva Lundberg for secretarial assistance. This study was supported by grants from Jeanssons Stiftelser, Stiftelsen Frimurare Barnhuset, Sällskapet Barnavård, Åke Wibergs Stiftelse, Magnus Bergvalls Stiftelse, Mary Béves Stiftelse, and the Swedish Foundation for Strategic Research, Vetenskaprådet. T.R. is supported by a grant from Märta och Gunnar V. Philipsons Stiftelse.
PY - 2005/11
Y1 - 2005/11
N2 - Wnt7a has been reported to signal via the canonical pathway, but also in non-canonical pathways acting on the cytoskeleton. Since Wnt7a is expressed after neurulation, we set to investigate the effects of Wnt7a on brain regionalization. We engineered transgenic mouse embryos that, under control of the nestin second intron, overexpressed Wnt7a in neural stem/progenitor cells. Surprisingly, transgenic embryos failed to complete cranial neurulation due to reduced levels and an impaired distribution of actin microfilaments, β-catenin, and N-cadherin at the neural tube adherens junctions. These transgenic embryos expressed high levels of Vangl2, an essential component of non-canonical Wnt signaling. In agreement with a disregulation of this pathway, aberrant spinal neurulation was detected in the transgenic embryos, revealing a novel function regulated by Wnts. Thus, our findings suggest that Wnt7a overexpression disrupts normal Wnt signaling in the neural tube, resulting in defective adherens junctions and neurulation. © 2005 Elsevier Inc. All rights reserved.
AB - Wnt7a has been reported to signal via the canonical pathway, but also in non-canonical pathways acting on the cytoskeleton. Since Wnt7a is expressed after neurulation, we set to investigate the effects of Wnt7a on brain regionalization. We engineered transgenic mouse embryos that, under control of the nestin second intron, overexpressed Wnt7a in neural stem/progenitor cells. Surprisingly, transgenic embryos failed to complete cranial neurulation due to reduced levels and an impaired distribution of actin microfilaments, β-catenin, and N-cadherin at the neural tube adherens junctions. These transgenic embryos expressed high levels of Vangl2, an essential component of non-canonical Wnt signaling. In agreement with a disregulation of this pathway, aberrant spinal neurulation was detected in the transgenic embryos, revealing a novel function regulated by Wnts. Thus, our findings suggest that Wnt7a overexpression disrupts normal Wnt signaling in the neural tube, resulting in defective adherens junctions and neurulation. © 2005 Elsevier Inc. All rights reserved.
KW - Actin Cytoskeleton/metabolism
KW - Proto-Oncogene Proteins/genetics
KW - Mice, Transgenic
KW - Neurons/cytology
KW - Signal Transduction/physiology
KW - Cell Adhesion/genetics
KW - Neural Tube Defects/genetics
KW - Adherens Junctions/metabolism
KW - Animals
KW - Nerve Tissue Proteins/metabolism
KW - Cell Communication/genetics
KW - Cadherins/metabolism
KW - beta Catenin/metabolism
KW - Gene Expression Regulation, Developmental/genetics
KW - Cell Differentiation/genetics
KW - Mice
KW - Wnt Proteins/genetics
KW - Up-Regulation/genetics
KW - Stem Cells/cytology
KW - Central Nervous System/cytology
UR - https://www.scopus.com/pages/publications/26244459125
UR - https://www.scopus.com/pages/publications/26244459125#tab=citedBy
UR - https://www.mendeley.com/catalogue/530e2a72-d437-3e62-ada6-e6cbaf58bacc/
U2 - 10.1016/j.mcn.2005.08.008
DO - 10.1016/j.mcn.2005.08.008
M3 - Article
C2 - 16154760
SN - 1044-7431
VL - 30
SP - 437
EP - 451
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
IS - 3
ER -