title: Synergistic regulation of cerebellar Purkinje neuron development by laminin epitopes and collagen on an artificial hybrid matrix construct.
abstract: The extracellular matrix (ECM) creates a dynamic environment around the cells in the developing central nervous system, providing them with the necessary biochemical and biophysical signals. Although the functions of many ECM molecules in neuronal development have been individually studied in detail, the combinatorial effects of multiple ECM components are not well characterized. Here we demonstrate that the expression of collagen and laminin-1 (lam-1) are spatially and temporally correlated during embryonic and post-natal development of the cerebellum. These changes in ECM distribution correspond to specific stages of Purkinje neuron (PC) migration, somatic monolayer formation and polarization. To clarify the respective roles of these ECM molecules on PC development, we cultured cerebellar neurons on a hybrid matrix comprised of collagen and a synthetic peptide amphiphile nanofiber bearing a potent lam-1 derived bioactive IKVAV peptide epitope. By systematically varying the concentration and ratio of collagen and the laminin epitope in the matrix, we could demonstrate a synergistic relationship between these two ECM components in controlling multiple aspects of PC maturation. An optimal ratio of collagen and IKVAV in the matrix was found to promote maximal PC survival and dendrite growth, while dendrite penetration into the matrix was enhanced by a high IKVAV to collagen ratio. In addition, the laminin epitope was found to guide PC axon development. By combining our observationsin vivoandin vitro, we propose a model of PC development where the synergistic effects of collagen and lam-1 play a key role in migration, polarization and morphological maturation of PCs.
authors.affiliation: Laboratory for Memory and Learning, RIKEN Brain Science Institute, Wako-shi, 351-0198 Saitama, Japan ; School of Medical Science and Technology, IIT Kharagpur, 721302, India ; The Institute for Bionanotechnology in Medicine (IBNAM), Northwestern University, Chicago, IL 60611, USA.
authors.forename: Shantanu
authors.initials: S
authors.lastname: Sur
authors.affiliation: The Institute for Bionanotechnology in Medicine (IBNAM), Northwestern University, Chicago, IL 60611, USA ; Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University, Ankara, 06800, Turkey.
authors.forename: Mustafa O
authors.initials: MO
authors.lastname: Guler
authors.affiliation: Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Webber
authors.affiliation: Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Eugene T
authors.initials: ET
authors.lastname: Pashuck
authors.affiliation: Laboratory for Memory and Learning, RIKEN Brain Science Institute, Wako-shi, 351-0198 Saitama, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Ito
authors.affiliation: The Institute for Bionanotechnology in Medicine (IBNAM), Northwestern University, Chicago, IL 60611, USA ; Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA ; Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA ; Department of Chemistry, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Stupp
authors.affiliation: Laboratory for Memory and Learning, RIKEN Brain Science Institute, Wako-shi, 351-0198 Saitama, Japan ; Launey Research Unit for Molecular Neurocybernetics, RIKEN Brain Science Institute, Wako-shi, 351-0198 Saitama, Japan.
authors.forename: Thomas
authors.initials: T
authors.lastname: Launey
keywords: Purkinje neurons; cerebellum; collagen; development; laminin-1; synergistic regulation