title: Calreticulin is a secreted BMP antagonist, expressed in Hensen's node during neural induction.
abstract: Hensen's node is the "organizer" of the avian and mammalian early embryo. It has many functions, including neural induction and patterning of the ectoderm and mesoderm. Some of the signals responsible for these activities are known but these do not explain the full complexity of organizer activity. Here we undertake a functional screen to discover new secreted factors expressed by the node at this time of development. Using a Signal Sequence Trap in yeast, we identify several candidates. Here we focus on Calreticulin. We show that in addition to its known functions in intracellular Calcium regulation and protein folding, Calreticulin is secreted, it can bind to BMP4 and act as a BMP antagonist in vivo and in vitro. Calreticulin is not sufficient to account for all organizer functions but may contribute to the complexity of its activity.
authors.affiliation: Department of Cell & Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Irene
authors.initials: I
authors.lastname: De Almeida
authors.affiliation: Department of Cell & Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Nidia M M
authors.initials: NMM
authors.lastname: Oliveira
authors.affiliation: Francis Crick Institute, Midland Road, London NW1 1AT, UK.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Randall
authors.affiliation: Francis Crick Institute, Midland Road, London NW1 1AT, UK.
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Hill
authors.affiliation: Genetics Institute, Boston, MA, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: McCoy
authors.affiliation: Department of Cell & Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Claudio D
authors.initials: CD
authors.lastname: Stern
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D037281:Calnexin / Q000378:metabolism; D037282:Calreticulin / Q000378:metabolism*; D002645:Chickens; D004627:Embryonic Induction; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D009417:Nerve Tissue / Q000196:embryology* / Q000378:metabolism*; D054258:Neural Plate / Q000196:embryology / Q000378:metabolism; D020897:Organizers, Embryonic / Q000378:metabolism*; D015398:Signal Transduction; D012995:Solubility
chemical_list: D019485:Bone Morphogenetic Proteins; D037282:Calreticulin; D037281:Calnexin; D005346:Fibroblast Growth Factors
keywords: Calcium-binding proteins; Calnexin; Chick embryo; Gastrulation; Neural plate; Neurulation; Phospho-Smad