Abstract

A family of neurite outgrowth-promoting factors has been characterized and each factor has been shown to be a complex of laminin and a heparan sulfate proteoglycan, in which laminin funcitons as a potent inducer of neurite outgrowth in an in vitro assay. The characterization of these factors will be completed, using electron microscopy. Possible reasons why laminin and neurite-outgrowth-promoting factors differ in their sensitivities to antibodies will be studied. The sites on laminin that are required for its actions on neurons will be identified and characterized. Efforts will be made to identify the receptors on neurons that mediate the actions of laminin. In particular, the role of a purified neuronal cell surface heparan sulfate proteoglycan that has been shown to bind laminin will be studied. Using a responsive cell line, PC12 cells primed by growth with NGF, some of the intreacellular changes caused by laminin will be identified and compared to those induced by Nerve Growth Factor. Antibodies to laminin, laminin-heparan sulfate proteoglycan complexes, and neuronal receptors will be used to characterize the role of neurite outgrowth-promoting-factors in mediating neuronal axon outgrowth on substrates and cells that growth cones encounter in vitro. Injections of antibodies into chick will be used to identify possible roles for LN in developing and in regenerating nerves.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS019090-05
Application #
3399095
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1986-04-01
Project End
1989-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
5
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Schettino, Luis F; Adamovich, Sergei V; Bagce, Hamid et al. (2015) Disruption of activity in the ventral premotor but not the anterior intraparietal area interferes with on-line correction to a haptic perturbation during grasping. J Neurosci 35:2112-7
Arnold, Thomas D; Niaudet, Colin; Pang, Mei-Fong et al. (2014) Excessive vascular sprouting underlies cerebral hemorrhage in mice lacking ?V?8-TGF? signaling in the brain. Development 141:4489-99
Ma, Shang; Kwon, Hyo Jun; Johng, Heidi et al. (2013) Radial glial neural progenitors regulate nascent brain vascular network stabilization via inhibition of Wnt signaling. PLoS Biol 11:e1001469
Arnold, Thomas D; Zang, Keling; Vallejo-Illarramendi, Ainara (2013) Deletion of integrin-linked kinase from neural crest cells in mice results in aortic aneurysms and embryonic lethality. Dis Model Mech 6:1205-12
Vallejo-Illarramendi, Ainara; Marciano, Denise K; Reichardt, Louis F (2013) A novel method that improves sensitivity of protein detection in PAGE and Western blot. Electrophoresis 34:1148-50
Arnold, Thomas D; Ferrero, Gina M; Qiu, Haiyan et al. (2012) Defective retinal vascular endothelial cell development as a consequence of impaired integrin *V*8-mediated activation of transforming growth factor-*. J Neurosci 32:1197-206
Warren, M Sloan; Bradley, William D; Gourley, Shannon L et al. (2012) Integrin ?1 signals through Arg to regulate postnatal dendritic arborization, synapse density, and behavior. J Neurosci 32:2824-34
Fujiwara, Hironobu; Ferreira, Manuela; Donati, Giacomo et al. (2011) The basement membrane of hair follicle stem cells is a muscle cell niche. Cell 144:577-89
Reichardt, Louis F; Prokop, Andreas (2011) Introduction: the role of extracellular matrix in nervous system development and maintenance. Dev Neurobiol 71:883-8
Quach, Navaline L; Biressi, Stefano; Reichardt, Louis F et al. (2009) Focal adhesion kinase signaling regulates the expression of caveolin 3 and beta1 integrin, genes essential for normal myoblast fusion. Mol Biol Cell 20:3422-35

Showing the most recent 10 out of 65 publications