title: The cell surface membrane proteins Cdo and Boc are components and targets of the Hedgehog signaling pathway and feedback network in mice.
abstract: Cdo and Boc encode cell surface Ig/fibronectin superfamily members linked to muscle differentiation. Data here indicate they are also targets and signaling components of the Sonic hedgehog (Shh) pathway. Although Cdo and Boc are generally negatively regulated by Hedgehog (HH) signaling, in the neural tube Cdo is expressed within the Shh-dependent floor plate while Boc expression lies within the dorsal limit of Shh signaling. Loss of Cdo results in a Shh dosage-dependent reduction of the floor plate. In contrast, ectopic expression of Boc or Cdo results in a Shh-dependent, cell autonomous promotion of ventral cell fates and a non-cell-autonomous ventral expansion of dorsal cell identities consistent with Shh sequestration. Cdo and Boc bind Shh through a high-affinity interaction with a specific fibronectin repeat that is essential for activity. We propose a model where Cdo and Boc enhance Shh signaling within its target field.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Tenzen
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Allen
authors.forename: Francesca
authors.initials: F
authors.lastname: Cole
authors.forename: Jong-Sun
authors.initials: JS
authors.lastname: Kang
authors.forename: Robert S
authors.initials: RS
authors.lastname: Krauss
authors.forename: Andrew P
authors.initials: AP
authors.lastname: McMahon
mesh_terms: D000818:Animals; D019556:COS Cells; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D002645:Chickens / Q000378:metabolism; D002522:Chlorocebus aethiops; D004622:Embryo, Mammalian / Q000166:cytology; D004625:Embryo, Nonmammalian; D025461:Feedback, Physiological; D005353:Fibronectins / Q000737:chemistry; D053823:Hedgehog Proteins; D007074:Immunoglobulin G / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: C474334:BOC protein, human; C510745:Boc protein, mouse; C510744:Cdon protein, mouse; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D053823:Hedgehog Proteins; D007074:Immunoglobulin G; D011956:Receptors, Cell Surface; C509239:SHH protein, human; D015534:Trans-Activators