title: The small leucine-rich repeat secreted protein Asporin induces eyes in Xenopus embryos through the IGF signalling pathway.
abstract: Small leucine-rich repeat proteoglycan (SLRP) family proteins play important roles in a number of biological events. Here, we demonstrate that the SLRP family member Asporin (ASPN) plays a crucial role in the early stages of eye development in Xenopus embryos. During embryogenesis, ASPN is broadly expressed in the neuroectoderm of the embryo. Overexpression of ASPN causes the induction of ectopic eyes. By contrast, blocking ASPN function with a morpholino oligonucleotide (ASPN-MO) inhibits eye formation, indicating that ASPN is an essential factor for eye development. Detailed molecular analyses revealed that ASPN interacts with insulin growth factor receptor (IGFR) and is essential for activating the IGF receptor-mediated intracellular signalling pathway. Moreover, ASPN perturbed the Wnt, BMP and Activin signalling pathways, suggesting that ASPN thereby creates a favourable environment in which the IGF signal can dominate. ASPN is thus a novel secreted molecule essential for eye induction through the coordination of multiple signalling pathways.
authors.affiliation: Ocular Biology and Therapeutic unit (ORBIT), Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Kristin
authors.initials: K
authors.lastname: Luehders
authors.affiliation: Ocular Biology and Therapeutic unit (ORBIT), Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK Developmental Biomedical Science, Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST), 8916-5, Takayama-cho, Ikoma 630-0192, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Sasai
authors.affiliation: Ocular Biology and Therapeutic unit (ORBIT), Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Hongorzul
authors.initials: H
authors.lastname: Davaapil
authors.affiliation: Department of Oncology, The Hutchison/MRC Research Centre, University of Cambridge, Hills Road, Cambridge CB2 2XZ, UK.
authors.forename: Maiko
authors.initials: M
authors.lastname: Kurosawa-Yoshida
authors.affiliation: Ocular Biology and Therapeutic unit (ORBIT), Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hiura
authors.affiliation: Ocular Biology and Therapeutic unit (ORBIT), Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Tara
authors.initials: T
authors.lastname: Brah
authors.affiliation: Ocular Biology and Therapeutic unit (ORBIT), Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK Department of Oncology, The Hutchison/MRC Research Centre, University of Cambridge, Hills Road, Cambridge CB2 2XZ, UK s.ohnuma@ucl.ac.uk.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Ohnuma
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005123:Eye / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D060172:Morpholinos / Q000235:genetics; D054258:Neural Plate / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D014981:Xenopus / Q000196:embryology*; D029867:Xenopus Proteins / Q000378:metabolism*
chemical_list: C000604584:Aspn protein, Xenopus; D016326:Extracellular Matrix Proteins; D060172:Morpholinos; D029867:Xenopus Proteins
keywords: ASPN; Anterior-posterior polarity; Eye induction; IGF; Xenopus