title: Serotonin signaling is required for Wnt-dependent GRP specification and leftward flow in Xenopus.
abstract: 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.
authors.affiliation: Institute of Zoology, University of Hohenheim, Garbenstrasse 30, 70593 Stuttgart, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Beyer
authors.forename: Michael
authors.initials: M
authors.lastname: Danilchik
authors.forename: Thomas
authors.initials: T
authors.lastname: Thumberger
authors.forename: Philipp
authors.initials: P
authors.lastname: Vick
authors.forename: Matthias
authors.initials: M
authors.lastname: Tisler
authors.forename: Isabelle
authors.initials: I
authors.lastname: Schneider
authors.forename: Susanne
authors.initials: S
authors.lastname: Bogusch
authors.forename: Philipp
authors.initials: P
authors.lastname: Andre
authors.forename: Bärbel
authors.initials: B
authors.lastname: Ulmer
authors.forename: Peter
authors.initials: P
authors.lastname: Walentek
authors.forename: Beate
authors.initials: B
authors.lastname: Niesler
authors.forename: Martin
authors.initials: M
authors.lastname: Blum
authors.forename: Axel
authors.initials: A
authors.lastname: Schweickert
mesh_terms: D000818:Animals; D036703:Blastula / Q000378:metabolism; D019521:Body Patterning; D004625:Embryo, Nonmammalian / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction; D060449:Wnt Signaling Pathway; D014981:Xenopus / Q000196:embryology* / Q000378:metabolism*; D029867:Xenopus Proteins / Q000378:metabolism
chemical_list: D029867:Xenopus Proteins; D012701:Serotonin