Sfrp1 and Sfrp2 regulate anteroposterior axis elongation and somite segmentation during mouse embryogenesis.
Regulation of Wnt signaling is essential for embryonic patterning. Sfrps are secreted Wnt antagonists that directly interact with the Wnt ligand to inhibit signaling. Here, we show that Sfrp1 and Sfrp2 are required for anteroposterior (AP) axis elongation and somitogenesis in the thoracic region during mouse embryogenesis. Double homozygous mutations in Sfrp1 and Sfrp2 lead to severe shortening of the thoracic region. By contrast, a homozygous mutation in one or the other exerts no effect on embryogenesis, indicating that Sfrp1 and Sfrp2 are functionally redundant. The defect of a shortened thoracic region appears to be the consequence of AP axis reduction and incomplete somite segmentation. The reduction in the AP axis is partially due to abnormalities in cell migration of pre-somitic mesoderm from the end of gastrulation. Aberrant somite segmentation is associated with altered oscillations of Notch signaling, as evidenced by abnormal Lfng and Hes7 expression during somitogenesis in the thoracic region. This study suggests that Wnt regulation by Sfrp1 and Sfrp2 is required for embryonic patterning.
Vertebrate Body Plan, Center for Developmental Biology, RIKEN Kobe, Chuou-ku, Kobe 650-0047, Japan.
Wataru
W
Satoh
Takafumi
T
Gotoh
Yasuhiko
Y
Tsunematsu
Shinichi
S
Aizawa
Akihiko
A
Shimono
D000818:Animals; D001369:Axons / Q000378:metabolism*; D001683:Biological Clocks; D019521:Body Patterning; D002454:Cell Differentiation; D002478:Cells, Cultured; D046149:Embryo Culture Techniques; D047108:Embryonic Development; D005121:Extremities / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D019170:Somites / Q000166:cytology / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D000094742:Secreted Frizzled-Related Proteins
D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch; D051153:Wnt Proteins; D051176:beta Catenin; C485539:Sfrp1 protein, mouse; D000094742:Secreted Frizzled-Related Proteins; C491628:Sfrp2 protein, mouse