Mechanism of nodal flow: a conserved symmetry breaking event in left-right axis determination.
The leftward flow in extraembryonic fluid is critical for the initial determination of the left-right axis of mouse embryos. It is unclear if this is a conserved mechanism among other vertebrates and how the directionality of the flow arises from the motion of cilia. In this paper, we show that rabbit and medakafish embryos also exhibit a leftward fluid flow in their ventral nodes. In all cases, primary monocilia present a clockwise rotational-like motion. Observations of defective ciliary dynamics in mutant mouse embryos support the idea that the posterior tilt of the cilia during rotational-like beating can explain the leftward fluid flow. Moreover, we show that this leftward flow may produce asymmetric distribution of exogenously introduced proteins, suggesting morphogen gradients as a subsequent mechanism of left-right axis determination. Finally, we experimentally and theoretically characterize under which conditions a morphogen gradient can arise from the flow.
Okada
Yasushi
Y
Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Tokyo, 113-0033, Japan.
Takeda
Sen
S
Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Tokyo, 113-0033, Japan.
Tanaka
Yosuke
Y
Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Tokyo, 113-0033, Japan.
Belmonte
Juan-Carlos Izpisúa
JI
Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037.
Hirokawa
Nobutaka
N
Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Tokyo, 113-0033, Japan. Electronic address: hirokawa@m.u-tokyo.ac.jp.
D000653:Amniotic Fluid / Q000502:physiology*; D000818:Animals; D005075:Biological Evolution; D001755:Blastocyst / Q000502:physiology / Q000648:ultrastructure; D019521:Body Patterning / Q000502:physiology*; D002478:Cells, Cultured; D002923:Cilia / Q000502:physiology* / Q000648:ultrastructure; D004622:Embryo, Mammalian / Q000196:embryology* / Q000648:ultrastructure; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000648:ultrastructure; D007839:Functional Laterality / Q000502:physiology*; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009990:Oryzias; D011817:Rabbits; D013045:Species Specificity