title: Generation of robust left-right asymmetry in the mouse embryo requires a self-enhancement and lateral-inhibition system.
abstract: The bilateral symmetry of the mouse embryo is broken by leftward fluid flow in the node. However, it is unclear how this directional flow is then translated into the robust, left side-specific Nodal gene expression that determines and coordinates left-right situs throughout the embryo. While manipulating Nodal and Lefty gene expression, we have observed phenomena that are indicative of the involvement of a self-enhancement and lateral-inhibition (SELI) system. We constructed a mathematical SELI model that not only simulates, but also predicts, experimental data. As predicted by the model, Nodal expression initiates even on the right side. These results indicate that directional flow represents an initial small difference between the left and right sides of the embryo, but is insufficient to determine embryonic situs. Nodal and Lefty are deployed as a SELI system required to amplify this initial bias and convert it into robust asymmetry.
authors.affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University and CREST/SORST, Japan Science and Technology Corporation, Suita, Osaka 565-0871, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakamura
authors.forename: Naoki
authors.initials: N
authors.lastname: Mine
authors.forename: Etsushi
authors.initials: E
authors.lastname: Nakaguchi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mochizuki
authors.forename: Masamichi
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Kenta
authors.initials: K
authors.lastname: Yashiro
authors.forename: Chikara
authors.initials: C
authors.lastname: Meno
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamada
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D003198:Computer Simulation; D004622:Embryo, Mammalian / Q000196:embryology*; D004627:Embryonic Induction; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005822:Genetic Vectors; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D055458:Left-Right Determination Factors; D051379:Mice; D008817:Mice, Mutant Strains; D008954:Models, Biological; D008962:Models, Theoretical; D055457:Nodal Protein; D009924:Organ Culture Techniques; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D000097577:Homeobox Protein PITX2
chemical_list: D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D055458:Left-Right Determination Factors; D055457:Nodal Protein; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D000097577:Homeobox Protein PITX2; C491117:Foxh1 protein, mouse; C526008:Nodal protein, mouse