Increased Wnt levels in the neural tube impair the function of adherens junctions during neurulation.
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, beta-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.
Shariatmadari
Maria
M
Neonatal unit, Department of Woman and Child Health, Astrid Lindgren Children's Hospital, Q2:09, Karolinska Institutet, S-171 76 Stockholm, Sweden.
Peyronnet
Julie
J
Papachristou
Panagiotis
P
Horn
Zachi
Z
Sousa
Kyle M
KM
Arenas
Ernest
E
Ringstedt
Thomas
T
D008841:Actin Cytoskeleton / Q000378:metabolism; D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D002450:Cell Communication / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009436:Neural Tube Defects / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D015820:Cadherins; C431577:Ltap protein, mouse; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; C490508:Wnt7a protein, mouse; D051176:beta Catenin