title: F-spondin regulates neuronal survival through activation of disabled-1 in the chicken ciliary ganglion.
abstract: The extracellular membrane-associated protein F-spondin has been implicated in cell-matrix and cell-cell adhesion and plays an important role in axonal pathfinding. We report here that F-spondin is expressed in non-neuronal cells in the embryonic chicken ciliary ganglion (CG) and robustly promotes survival of cultured CG neurons. Using deletion constructs of F-spondin we found that the amino-terminal Reelin/Spondin domain cooperates with thrombospondin type 1 repeat (TSR) 6, a functional TGFβ-activation domain. In ovo treatment with blocking antibodies raised against the Reelin/Spondin domain or the TSR-domains caused increased apoptosis of CG neurons during the phase of programmed cell death and loss of about 30% of the neurons compared to controls. The Reelin/Spondin domain receptor - APP and its downstream signalling molecule disabled-1 are expressed in CG neurons. F-spondin induced rapid phosphorylation of disabled-1. Moreover, both blocking the central APP domain and interference with disabled-1 signalling disrupted the survival promoting effect of F-spondin. Taken together, our data suggest that F-spondin can promote neuron survival by a mechanism involving the Reelin/Spondin and the TSR domains.
authors.affiliation: Neuroanatomy & Interdisciplinary Center for Neurosiences (IZN), University of Heidelberg, Heidelberg, Germany. h.peterziel@dkfz.de
authors.forename: H
authors.initials: H
authors.lastname: Peterziel
authors.forename: T
authors.initials: T
authors.lastname: Sackmann
authors.forename: J
authors.initials: J
authors.lastname: Strelau
authors.forename: P H
authors.initials: PH
authors.lastname: Kuhn
authors.forename: S F
authors.initials: SF
authors.lastname: Lichtenthaler
authors.forename: K
authors.initials: K
authors.lastname: Marom
authors.forename: A
authors.initials: A
authors.lastname: Klar
authors.forename: K
authors.initials: K
authors.lastname: Unsicker
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002470:Cell Survival; D002642:Chick Embryo; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005726:Ganglia, Parasympathetic / Q000196:embryology / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D000091042:Reelin Protein; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human