TY - JOUR
T1 - Wnt signaling regulates left-right axis formation in the node of mouse embryos
AU - Kitajima, Keiko
AU - Oki, Shinya
AU - Ohkawa, Yasuyuki
AU - Sumi, Tomoyuki
AU - Meno, Chikara
N1 - Funding Information:
We thank Y. Honda and Y. Nakajo for technical assistance; S. Nonaka for advice on observation of nodal flow; H. Sasaki, P. Chambon, T. Honjo, and S. Nagata for providing expression vectors; and S. Creekmore for providing recombineering reagents. The NICD expression plasmid was provided by the RIKEN BRC through the National Bio-Resource Project of the Ministry of Education, Culture, Sports, Science, and Technology of Japan. We also appreciate the technical support provided by the Research Support Center, Graduate School of Medical Sciences, Kyushu University. This work was supported by KAKENHI grants 21116002 , 23570233 , and 23770254 from the Japan Society for the Promotion of Science.
PY - 2013/8/15
Y1 - 2013/8/15
N2 - The node triggers formation of the left-right axis in mouse embryos by establishing local asymmetry of Nodal and Cerl2 expression. We found that Wnt3 is expressed in perinodal crown cells preferentially on the left side. The enhancer responsible for Wnt3 expression was identified and found to be regulated by Foxa2 and Rbpj under the control of Notch signaling. Rbpj binding sites suppress enhancer activity in pit cells of the node, thereby ensuring crown cell-specific expression. In addition, we found that the expression of Gdf1 and Cerl2 is also regulated by Notch signaling, suggesting that such signaling may induce the expression of genes related to left-right asymmetry as a set. Furthermore, Cerl2 expression became symmetric in response to inhibition of Wnt-β-catenin signaling. Our results suggest that Wnt signaling regulates the asymmetry of Cerl2 expression, which likely generates a left-right difference in Nodal activity at the node for further amplification in lateral plate mesoderm.
AB - The node triggers formation of the left-right axis in mouse embryos by establishing local asymmetry of Nodal and Cerl2 expression. We found that Wnt3 is expressed in perinodal crown cells preferentially on the left side. The enhancer responsible for Wnt3 expression was identified and found to be regulated by Foxa2 and Rbpj under the control of Notch signaling. Rbpj binding sites suppress enhancer activity in pit cells of the node, thereby ensuring crown cell-specific expression. In addition, we found that the expression of Gdf1 and Cerl2 is also regulated by Notch signaling, suggesting that such signaling may induce the expression of genes related to left-right asymmetry as a set. Furthermore, Cerl2 expression became symmetric in response to inhibition of Wnt-β-catenin signaling. Our results suggest that Wnt signaling regulates the asymmetry of Cerl2 expression, which likely generates a left-right difference in Nodal activity at the node for further amplification in lateral plate mesoderm.
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U2 - 10.1016/j.ydbio.2013.05.011
DO - 10.1016/j.ydbio.2013.05.011
M3 - Article
C2 - 23707899
AN - SCOPUS:84879890158
SN - 0012-1606
VL - 380
SP - 222
EP - 232
JO - Developmental Biology
JF - Developmental Biology
IS - 2
ER -