title: Chick CFC controls Lefty1 expression in the embryonic midline and nodal expression in the lateral plate.
abstract: Members of the EGF-CFC family of proteins have recently been implicated as essential cofactors for Nodal signaling. Here we report the isolation of chick CFC and describe its expression pattern, which appears to be similar to Cfc1 in mouse. During early gastrulation, chick CFC was asymmetrically expressed on the left side of Hensen's node as well as in the emerging notochord, prechordal plate, and lateral plate mesoderm. Subsequently, its expression became confined to the heart fields, notochord, and posterior mesoderm. Implantation experiments suggest that chick CFC expression in the lateral plate mesoderm is dependent on BMP signaling, while in the midline its expression depends on an Activin-like signal. The asymmetric expression domain within Hensen's node was not affected by application of FGF8, Noggin, or Shh antibody. Implantation of cells expressing human or mouse CFC2, or chick CFC on the right side of Hensen's node randomized heart looping without affecting expression of genes involved in left-right axis formation, including SnR, Nodal, Car, or Pitx2. Application of antisense oligodeoxynucleotides to the midline of Hamburger-Hamilton stage 4-5 embryos also randomized heart looping, but in contrast to the overexpression experiments, antisense oligodeoxynucleotide treatment resulted in bilateral expression of Nodal, Car, Pitx2, and NKX3.2, whereas Lefty1 expression in the midline was transiently lost. Application of the antisense oligodeoxynucleotides to the lateral plate mesoderm abolished Nodal expression. Thus, chick CFC seems to have a dual function in left-right axis formation by maintaining Nodal expression in the lateral plate mesoderm and controlling expression of Lefty1 expression in the midline territory.
authors.affiliation: Department of Cell and Molecular Biology, Technical University of Braunschweig, Braunschweig, 38106, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Schlange
authors.forename: I
authors.initials: I
authors.lastname: Schnipkoweit
authors.forename: B
authors.initials: B
authors.lastname: Andrée
authors.forename: A
authors.initials: A
authors.lastname: Ebert
authors.forename: M H
authors.initials: MH
authors.lastname: Zile
authors.forename: H H
authors.initials: HH
authors.lastname: Arnold
authors.forename: T
authors.initials: T
authors.lastname: Brand
mesh_terms: D000818:Animals; D019521:Body Patterning; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002642:Chick Embryo; D003370:Coturnix / Q000196:embryology; D004815:Epidermal Growth Factor / Q000235:genetics; D058851:GPI-Linked Proteins; D018507:Gene Expression Regulation, Developmental; D006133:Growth Substances / Q000235:genetics; D006321:Heart / Q000196:embryology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D055458:Left-Right Determination Factors; D008562:Membrane Glycoproteins; D008648:Mesoderm; D051379:Mice; D008954:Models, Biological; D009024:Morphogenesis; D009363:Neoplasm Proteins / Q000235:genetics; D055457:Nodal Protein; D009672:Notochord; D020897:Organizers, Embryonic; D011506:Proteins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
chemical_list: D019485:Bone Morphogenetic Proteins; C431069:CFC protein, chicken; C491268:CFC1 protein, human; C104433:Cfc1 protein, mouse; D058851:GPI-Linked Proteins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; C526161:LEFTY1 protein, human; D055458:Left-Right Determination Factors; D008562:Membrane Glycoproteins; C526007:NODAL protein, human; D009363:Neoplasm Proteins; D055457:Nodal Protein; C526008:Nodal protein, mouse; D011506:Proteins; C070636:TDGF1 protein, human; C489450:Tdgf1 protein, mouse; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor