title: N-cadherin locks left-right asymmetry by ending the leftward movement of Hensen's node cells.
abstract: The stereotypic left-right (LR) asymmetric distribution of internal organs is due to an asymmetric molecular cascade in the lateral plate mesoderm (LPM) that is originated at the embryonic node. In chicken embryos, molecular asymmetries at Hensen's node are created by leftward cell movements that occur transiently. What terminates these movements, and, moreover, what is the impact of prolonging them on the LR asymmetry cascade? We show that leftward movements last longer when N-cadherin function is blocked and cease prematurely when N-cadherin is overexpressed on the right side of the node. The prolonged leftward movements lead to loss of asymmetric expression of fgf8 and nodal at the node region. This originates an abnormal expression of the asymmetric genes cer1 and snai1 in the LPM, resulting in mispositioned hearts. We conclude that N-cadherin stops the leftward cell movements and that this termination is an essential step in the establishment of LR asymmetry.
authors.affiliation: Instituto de Medicina Molecular e Instituto de Histologia e Biologia do Desenvolvimento, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal.
authors.forename: Raquel V
authors.initials: RV
authors.lastname: Mendes
authors.affiliation: Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal; Centro de Biologia Ambiental, Faculdade de Ciências da Universidade de Lisboa, 1749-016 Lisboa, Portugal.
authors.forename: Gabriel G
authors.initials: GG
authors.lastname: Martins
authors.affiliation: Instituto de Medicina Molecular e Instituto de Histologia e Biologia do Desenvolvimento, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Cristovão
authors.affiliation: Instituto de Medicina Molecular e Instituto de Histologia e Biologia do Desenvolvimento, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal. Electronic address: msaude@fm.ul.pt.
authors.forename: Leonor
authors.initials: L
authors.lastname: Saúde
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D015820:Cadherins / Q000378:metabolism*; D002642:Chick Embryo; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006321:Heart / Q000196:embryology; D053823:Hedgehog Proteins / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism; D020897:Organizers, Embryonic / Q000196:embryology*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D015820:Cadherins; D053823:Hedgehog Proteins