title: [Establishment of visceral left-right asymmetry in mammals: the role of ciliary action and leftward fluid flow in the region of Hensen's node].
abstract: During individual development of vertebrates, the anteroposterior, dorsoventral, and left-right axes of the body are established. Although the vertebrates are bilaterally symmetric outside, their internal structure is asymmetric. Of special interest is the insight into establishment of visceral left-right asymmetry in mammals, since it has not only basic but also an applied medical significance. As early as 1976, it was hypothesized that the ciliary action could be associated with the establishment of left-right asymmetry in mammals. Currently, the majority of researchers agree that the ciliary action in the region of Hensen's node and the resulting leftward laminar fluid flow play a key role in the loss of bilateral symmetry and triggering of expression of the genes constituting the Nodal-Ptx2 signaling cascade, specific of the left side of the embryo. The particular mechanism underlying this phenomenon is still insufficiently clear. There are three competing standpoints on how leftward fluid flow induces expression of several genes in the left side of the embryo. The morphogen gradient hypothesis postulates that the leftward flow creates a high concentration of a signaling biomolecule in the left side of Hensen's node, which, in turn, stimulates triggering of.gene expression of the Nodal-Ptx2 cascade. The biomechanical hypothesis (or two-cilia model) states that the immotile cilia located in the periphery of Hensen's node act as mechanosensors, activate mechanosensory ion channels, and trigger calcium signaling in the left side of the embryo. Finally, the "shuttle-bus model" holds that leftward fluid flow carries the lipid vesicles, which are crashed when colliding immotile cilia in the periphery of Hensen's node to release the contained signaling biomolecules. It is also noteworthy that the association between the ciliary action and establishment of asymmetry has been recently discovered in representatives of the lower invertebrates. In this paper, the author considers evolution of concepts on the mechanisms underlying establishment of visceral left-right asymmetry since 1976 until the present and critically reexamines the current concepts in this field of science. According to the author, serious arguments favoring the biomechanical hypothesis for determination of left-right asymmetry in mammals have been obtained.
authors.forename: A S
authors.initials: AS
authors.lastname: Ermakov
mesh_terms: D000818:Animals; D002923:Cilia / Q000378:metabolism; D004622:Embryo, Mammalian / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D009024:Morphogenesis / Q000502:physiology*; D055457:Nodal Protein / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C526007:NODAL protein, human; D055457:Nodal Protein