Genetic interaction between Lrp6 and Wnt5a during mouse development.
Lrp6 is generally described as a receptor required for signal transduction in the Wnt/beta-catenin pathway. Wnt5a, however, is a Wnt ligand that usually does not activate Wnt/beta-catenin but rather activates noncanonical Wnt signaling. We have previously shown that Lrp6 can inhibit noncanonical Wnt5a/Wnt11 signaling and that Lrp5/6 loss-of-function produces noncanonical gain-of function defects, which can be rescued by loss of Wnt5a. Here, we describe other phenotypes found in Wnt5a/Lrp6 compound mutant mice, including a worsening of individual Wnt5a or Lrp6 loss of function phenotypes. Lrp6 haploinsufficiency in a Wnt5a-/- background caused spina bifida and exacerbated posterior truncation. Wnt5a-/-Lrp6-/- embryos displayed presomitic mesoderm morphogenesis, somitogenesis, and neurogenesis defects, which are much more severe than in either of the single mutants. Interestingly these results reveal a further level of complexity in processes in which Wnt5a and LRP6 cooperate, or oppose each other, during mouse development.
Molecular Neurobiology, Department of Medical Biochemistry & Biophysics, Karolinska Institutet, Stockholm, Sweden.
Emma R
ER
Andersson
Lenka
L
Bryjova
Kristin
K
Biris
Terry P
TP
Yamaguchi
Ernest
E
Arenas
Vítezslav
V
Bryja
D000818:Animals; D017931:DNA Primers / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics* / Q000502:physiology; D005838:Genotype; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D026502:LDL-Receptor Related Proteins / Q000235:genetics / Q000378:metabolism*; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D008648:Mesoderm / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout; D054259:Neural Tube / Q000196:embryology*; D010641:Phenotype; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D000071818:Wnt-5a Protein
D017931:DNA Primers; D026502:LDL-Receptor Related Proteins; D060488:Low Density Lipoprotein Receptor-Related Protein-6; C555476:Lrp6 protein, mouse; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse