Premium
Expression of α5 integrin rescues fibronectin responsiveness in NT2N CNS neuronal cells
Author(s) -
Meland Marit N.,
Herndon Mary E.,
Stipp Christopher S.
Publication year - 2010
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22171
Subject(s) - fibronectin , biology , integrin , microbiology and biotechnology , extracellular matrix , neurite , regeneration (biology) , central nervous system , cellular differentiation , cell , neuroscience , in vitro , genetics , gene
The extracellular matrix protein fibronectin is implicated in neuronal regeneration in the peripheral nervous system. In the central nervous system (CNS), fibronectin is up‐regulated at sites of penetrating injuries and stroke; however, CNS neurons down‐regulate the fibronectin receptor α5β1 integrin during differentiation and generally respond poorly to fibronectin. NT2N CNS neuron‐like cells (derived from NT2 precursor cells) have been used in preclinical and clinical studies for treatment of stroke and a variety of CNS injury and disease models. Here we show that, like primary CNS neurons, NT2N cells down‐regulate α5β1 integrin during differentiation and respond poorly to fibronectin. The poor neurite outgrowth by NT2N cells on fibronectin can be rescued by transducing NT2 precursors with a retroviral vector expressing α5 integrin under the control of the murine stem cell virus 5′ long terminal repeat. Sustained α5 integrin expression is compatible with the CNS‐like neuronal differentiation of NT2N cells and does not prevent robust neurite outgrowth on other integrin ligands. Thus, α5 integrin expression in CNS neuronal precursor cells may provide a strategy for enhancing the outgrowth and survival of implanted cells in cell‐replacement therapies for CNS injury and disease. © 2009 Wiley‐Liss, Inc.