NEDD4L regulates convergent extension movements in Xenopus embryos via Disheveled-mediated non-canonical Wnt signaling.
During the early vertebrate body plan formation, convergent extension (CE) of dorsal mesoderm and neurectoderm is coordinated by the evolutionarily conserved non-canonical Wnt/PCP signaling. Disheveled (Dvl), a key mediator of Wnt/PCP signaling, is essential for the medial-lateral polarity formation in the cells undergoing convergent extension movements. NEDD4L, a highly conserved HECT type E3 ligase, has been reported to regulate the stability of multiple substrates including Dvl2. Here we demonstrate that NEDD4L is required for the cellular polarity formation and convergent extension in the early Xenopus embryos. Depletion of NEDD4L in early Xenopus embryos results in the loss of mediolateral polarity of the convergent-extending mesoderm cells and the shortened body axis, resembling those defects caused by the disruption of non-canonical Wnt signaling. Depletion of xNEDD4L also blocks the elongation of the animal explants in response to endogenous mesoderm inducing signals and partially compromises the expression of Brachyury. Importantly, reducing Dvl2 expression can largely rescue the cellular polarity and convergent extension defects in NEDD4L-depleted embryos and explants. Together with the data that NEDD4L reduces Dvl2 protein expression in the frog embryos, our findings suggest that regulation of Dvl protein levels by NEDD4L is essential for convergent extension during early Xenopus embryogenesis.
The State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China; School of Life Sciences, Tsinghua University, Beijing 100084, China.
Yan
Y
Zhang
The State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China; School of Life Sciences, Tsinghua University, Beijing 100084, China.
Yi
Y
Ding
The State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: ygchen@tsinghua.edu.cn.
Ye-Guang
YG
Chen
School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: qhtaolab@tsinghua.edu.cn.
Qinghua
Q
Tao
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D002460:Cell Line; D016764:Cell Polarity / Q000502:physiology; D000072261:Dishevelled Proteins; D004625:Embryo, Nonmammalian / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000502:physiology*; D005326:Fetal Proteins / Q000096:biosynthesis; D054262:Gastrulation / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D008648:Mesoderm / Q000166:cytology / Q000196:embryology; D060172:Morpholinos / Q000235:genetics; D000075702:Nedd4 Ubiquitin Protein Ligases; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D020825:T-Box Domain Proteins / Q000096:biosynthesis / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000502:physiology*; D060449:Wnt Signaling Pathway; D029867:Xenopus Proteins / Q000096:biosynthesis / Q000235:genetics; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000098908:Brachyury Protein
D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D005326:Fetal Proteins; D060172:Morpholinos; D000075702:Nedd4 Ubiquitin Protein Ligases; D010750:Phosphoproteins; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D044767:Ubiquitin-Protein Ligases; D029867:Xenopus Proteins; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein; D000098908:Brachyury Protein; C000606586:DVL1 protein, Xenopus; C000606581:DVL2 protein, human; C116765:TBXT protein, Xenopus; C000618485:Nedd4L protein, human; C000618460:nedd4l protein, Xenopus
Convergent-extension; Dishevelled; NEDD4L