title: Scaling of dorsal-ventral patterning by embryo size-dependent degradation of Spemann's organizer signals.
abstract: Spemann's organizer plays a key role in dorsal-ventral (DV) patterning in the amphibian embryo by secreting diffusible proteins such as Chordin, an antagonist to ventralizing bone morphogenetic proteins (BMPs). The DV patterning is so robust that an amphibian embryo with its ventral half surgically removed can develop into a smaller but proportionally patterned larva. Here, we show that this robust patterning depends on facilitated Chordin degradation and requires the expression of the Chordin-proteinase inhibitor Sizzled on the opposite side. Sizzled, which is stable and diffuses widely along the DV axis, stabilizes Chordin and expands its distribution in the ventral direction. This expanded Chordin distribution, in turn, limits BMP-dependent Sizzled production, forming an axis-wide feedback loop for shaping Chordin's activity. Using bisection assays, we demonstrate that Chordin degradation is dynamically controlled by embryo-size-coupled Sizzled accumulation. We propose a scaling model that enables the DV pattern to adjust proportionally to embryonic axis size.
authors.affiliation: Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan. hideino@cdb.riken.jp
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Inomata
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Shibata
authors.forename: Tomoko
authors.initials: T
authors.lastname: Haraguchi
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sasai
mesh_terms: D000818:Animals; D019521:Body Patterning; D049628:Body Size; D004625:Embryo, Nonmammalian / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D020897:Organizers, Embryonic / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology*
chemical_list: D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D029867:Xenopus Proteins; C109976:szl protein, Xenopus; C054234:chordin