Sfrp1, Sfrp2, and Sfrp5 regulate the Wnt/beta-catenin and the planar cell polarity pathways during early trunk formation in mouse.
Sfrp is a secreted Wnt antagonist that directly interacts with Wnt ligand. We show here that inactivation of Sfrp1, Sfrp2, and Sfrp5 leads to fused somites formation in early-somite mouse embryos, simultaneously resulting in defective convergent extension (CE), which causes severe shortening of the anteroposterior axis. These observations indicate the redundant roles of Sfrp1, Sfrp2, and Sfrp5 in early trunk formation. The roles of the Sfrps were genetically distinguished in terms of the regulation of Wnt pathways. Genetic analysis combining Sfrps mutants and Loop-tail mice revealed the involvement of Sfrps in CE through the regulation of the planar cell polarity pathway. Furthermore, Dkk1-deficient embryos carrying Sfrp1 homozygous and Sfrp2 heterozygous mutations display irregular somites and indistinct intersomitic boundaries, which indicates that Sfrps-mediated inhibition of the Wnt/beta-catenin pathway is necessary for somitogenesis. Our results suggest that Sfrps regulation of the canonical and noncanonical pathways is essential for proper trunk formation.
Satoh
Wataru
W
Vertebrate Body Plan, Center for Developmental Biology, RIKEN Kobe, Minatojima-Minami, Chuou-ku, Kobe, Japan.
Matsuyama
Makoto
M
Takemura
Hiromasa
H
Aizawa
Shinichi
S
Shimono
Akihiko
A
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019521:Body Patterning; D016764:Cell Polarity; D004622:Embryo, Mammalian / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D019170:Somites / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D000094742:Secreted Frizzled-Related Proteins
D048868:Adaptor Proteins, Signal Transducing; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051153:Wnt Proteins; D051176:beta Catenin; C485539:Sfrp1 protein, mouse; D000094742:Secreted Frizzled-Related Proteins; C491628:Sfrp2 protein, mouse; C487972:Sfrp5 protein, mouse