TY - JOUR
T1 - Serotonin signaling is required for Wnt-dependent GRP specification and leftward flow in Xenopus
AU - Beyer, Tina
AU - Danilchik, Michael
AU - Thumberger, Thomas
AU - Vick, Philipp
AU - Tisler, Matthias
AU - Schneider, Isabelle
AU - Bogusch, Susanne
AU - Andre, Philipp
AU - Ulmer, Bärbel
AU - Walentek, Peter
AU - Niesler, Beate
AU - Blum, Martin
AU - Schweickert, Axel
N1 - Funding Information:
Work in the M.B. lab was supported by a grant from the Deutsche Forschungsgemeinschaft (BL-285/9), and M.D.'s research is funded by the National Science Foundation (IOS 0921415). P.V., T.T., T.B., B.U., and P.W. were recipients of Ph.D. fellowships from the Landesgraduiertenförderung Baden-Württemberg. We thank Michael Levin, Randy Moon, Janet Heasman, Chris Kintner, Herbert Steinbeisser, and Jean Lauder for plasmids and antibodies, Christof Niehrs for communicating unpublished results, and Werner Amselgruber for help with SEM analysis.
PY - 2012/1/10
Y1 - 2012/1/10
N2 - In vertebrates, most inner organs are asymmetrically arranged with respect to the main body axis [1]. Symmetry breakage in fish, amphibian, and mammalian embryos depends on cilia-driven leftward flow of extracellular fluid during neurulation [2-5]. Flow induces the asymmetric nodal cascade that governs asymmetric organ morphogenesis and placement [1, 6, 7]. In the frog Xenopus, an alternative laterality-generating mechanism involving asymmetric localization of serotonin at the 32-cell stage has been proposed [8]. However, no functional linkage between this early localization and flow at neurula stage has emerged. Here, we report that serotonin signaling is required for specification of the superficial mesoderm (SM), which gives rise to the ciliated gastrocoel roof plate (GRP) where flow occurs [5, 9]. Flow and asymmetry were lost in embryos in which serotonin signaling was downregulated. Serotonin, which we found uniformly distributed along the main body axes in the early embryo, was required for Wnt signaling, which provides the instructive signal to specify the GRP. Importantly, serotonin was required for Wnt-induced double-axis formation as well. Our data confirm flow as primary mechanism of symmetry breakage and suggest a general role of serotonin as competence factor for Wnt signaling during axis formation in Xenopus.
AB - In vertebrates, most inner organs are asymmetrically arranged with respect to the main body axis [1]. Symmetry breakage in fish, amphibian, and mammalian embryos depends on cilia-driven leftward flow of extracellular fluid during neurulation [2-5]. Flow induces the asymmetric nodal cascade that governs asymmetric organ morphogenesis and placement [1, 6, 7]. In the frog Xenopus, an alternative laterality-generating mechanism involving asymmetric localization of serotonin at the 32-cell stage has been proposed [8]. However, no functional linkage between this early localization and flow at neurula stage has emerged. Here, we report that serotonin signaling is required for specification of the superficial mesoderm (SM), which gives rise to the ciliated gastrocoel roof plate (GRP) where flow occurs [5, 9]. Flow and asymmetry were lost in embryos in which serotonin signaling was downregulated. Serotonin, which we found uniformly distributed along the main body axes in the early embryo, was required for Wnt signaling, which provides the instructive signal to specify the GRP. Importantly, serotonin was required for Wnt-induced double-axis formation as well. Our data confirm flow as primary mechanism of symmetry breakage and suggest a general role of serotonin as competence factor for Wnt signaling during axis formation in Xenopus.
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U2 - 10.1016/j.cub.2011.11.027
DO - 10.1016/j.cub.2011.11.027
M3 - Article
C2 - 22177902
AN - SCOPUS:84855672231
SN - 0960-9822
VL - 22
SP - 33
EP - 39
JO - Current Biology
JF - Current Biology
IS - 1
ER -