NF2/Merlin is required for the axial pattern formation in the Xenopus laevis embryo.
The NF2 gene product Merlin is a FERM-domain protein possessing a broad tumor-suppressing function. NF2/Merlin has been implicated in regulating multiple signaling pathways critical for cell growth and survival. However, it remains unknown whether NF2/Merlin regulates Wnt/β-catenin signaling during vertebrate embryogenesis. Here we demonstrate that NF2/Merlin is required for body pattern formation in the Xenopus laevis embryo. Depletion of the maternal NF2/Merlin enhances organizer gene expression dependent on the presence of β-catenin, and causes dorsanteriorized development; Morpholino antisense oligo-mediated knockdown of the zygotic NF2/Merlin shifts posterior genes anteriorwards and reduces the anterior development. We further demonstrate that targeted depletion of NF2 in the presumptive dorsal tissues increases the levels of nuclear β-catenin in the neural epithelial cells. Biochemical analyses reveal that NF2 depletion promotes the production of active β-catenin and concurrently decreases the level of N-terminally phosphorylated β-catenin under the stimulation of the endogenous Wnt signaling. Our findings suggest that NF2/Merlin negatively regulates the Wnt/β-catenin signaling activity during the pattern formation in early X. laevis embryos.
The MOE Key Laboratory of Protein Sciences, Tsinghua University School of Life Sciences, Beijing 10084, China.
Xuechen
X
Zhu
The MOE Key Laboratory of Protein Sciences, Tsinghua University School of Life Sciences, Beijing 10084, China.
Zheying
Z
Min
The MOE Key Laboratory of Protein Sciences, Tsinghua University School of Life Sciences, Beijing 10084, China.
Renbo
R
Tan
The MOE Key Laboratory of Protein Sciences, Tsinghua University School of Life Sciences, Beijing 10084, China. Electronic address: qhtaolab@tsinghua.edu.cn.
Qinghua
Q
Tao
D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055786:Gene Knockout Techniques; D016515:Genes, Neurofibromatosis 2; D017403:In Situ Hybridization; D008297:Male; D025581:Neurofibromin 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000235:genetics; D009865:Oocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway; D029867:Xenopus Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000502:physiology*; D015053:Zygote / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
C495266:CTNNB1 protein, Xenopus; D025581:Neurofibromin 2; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D029867:Xenopus Proteins; D051176:beta Catenin
AP patterning; NF2/Merlin; Spemann organizer; Wnt signaling; Xenopus; β-catenin