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ID 115884
著者
Kawamura, Nobuyuki Doshisha Women’s College of Liberal Arts
Hamada, Hiroshi RIKEN|Osaka University
Hadjantonakis, Anna-Katerina Memorial Sloan Kettering Cancer Center
Sun-Wada, Ge-Hong Doshisha Women’s College of Liberal Arts
Wada, Yoh Osaka University
資料タイプ
学術雑誌論文
抄録
Endocytosis has been proposed to modulate cell signaling activities. However, the role of endocytosis in embryogenesis, which requires coordination of multiple signaling inputs, has remained less understood. We previously showed that mouse embryos lacking a small guanosine triphosphate (GTP)-binding protein Rab7 implicated in endocytic flow are defective in gastrulation. Here, we investigate how subcellular defects associated with Rab7 deficiency are related to the observed developmental defects. Rab7-deficient embryos fail to organize mesodermal tissues due to defects in Wnt-β-catenin signaling. Visceral endoderm (VE)-specific ablation of Rab7 results in patterning defects similar to systemic Rab7 deletion. Rab7 mutants accumulate the Wnt antagonist Dkk1 in the extracellular space and in intracellular compartments throughout the VE epithelium. These data indicate that Rab7-dependent endocytosis regulates the concentration and availability of extracellular Dkk1, thereby relieving the epiblast of antagonism. This intercellular mechanism therefore organizes distinct spatiotemporal patterns of canonical Wnt activity during the peri-gastrulation stages of embryonic development.
掲載誌名
Cell Reports
ISSN
22111247
出版者
Elsevier
31
10
開始ページ
107733
発行日
2020-06-09
権利情報
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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フルテキストファイル
言語
eng
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出版社版
部局
先端酵素学研究所