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@ARTICLE{Lee:287615,
      author       = {H. Lee$^*$ and C. M. Camuto$^*$ and C. Niehrs$^*$},
      title        = {{R}-{S}pondin 2 governs {X}enopus left-right body axis
                      formation by establishing an {FGF} signaling gradient.},
      journal      = {Nature Communications},
      volume       = {15},
      number       = {1},
      issn         = {2041-1723},
      address      = {[London]},
      publisher    = {Nature Publishing Group UK},
      reportid     = {DKFZ-2024-00269},
      pages        = {1003},
      year         = {2024},
      note         = {DKFZ-ZMBH Alliance / #EA:A050#LA:A050#},
      abstract     = {Establishment of the left-right (LR, sinistral, dextral)
                      body axis in many vertebrate embryos relies on cilia-driven
                      leftward fluid flow within an LR organizer (LRO). A cardinal
                      question is how leftward flow triggers symmetry breakage.
                      The chemosensation model posits that ciliary flow enriches a
                      signaling molecule on the left side of the LRO that promotes
                      sinistral cell fate. However, the nature of this
                      sinistralizing signal has remained elusive. In the Xenopus
                      LRO, we identified the stem cell growth factor R-Spondin 2
                      (Rspo2) as a symmetrically expressed, sinistralizing signal.
                      As predicted for a flow-mediated signal, Rspo2 operates
                      downstream of leftward flow but upstream of the
                      asymmetrically expressed gene dand5. Unexpectedly, in LR
                      patterning, Rspo2 acts as an FGF receptor antagonist: Rspo2
                      via its TSP1 domain binds Fgfr4 and promotes its membrane
                      clearance by Znrf3-mediated endocytosis. Concordantly, we
                      find that at flow-stage, FGF signaling is dextralizing and
                      forms a gradient across the LRO, high on the dextral- and
                      low on the sinistral side. Rspo2 gain- and loss-of function
                      equalize this FGF signaling gradient and sinistralize and
                      dextralize development, respectively. We propose that
                      leftward flow of Rspo2 produces an FGF signaling gradient
                      that governs LR-symmetry breakage.},
      cin          = {A050},
      ddc          = {500},
      cid          = {I:(DE-He78)A050-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38307837},
      doi          = {10.1038/s41467-024-44951-7},
      url          = {https://inrepo02.dkfz.de/record/287615},
}