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The Journal of Neuroscience, July 23, 2003, 23(16):6638-6650
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A New Role for the Cell Adhesion Molecule L1 in Neural Precursor Cell Proliferation, Differentiation, and Transmitter-Specific Subtype Generation
Marcel Dihné,1
Christian Bernreuther,1
Mirjam Sibbe,1
Werner Paulus,2 and
Melitta Schachner1
1Zentrum für Molekulare Neurobiologie
Hamburg, Universität Hamburg, D-20251 Hamburg, Germany, and
2Institut für Neuropathologie, Universität
Münster, D-48129 Münster, Germany
Adhesion molecules play important roles in the development and regeneration
of the CNS and PNS. We found that the immunoglobulin superfamily recognition
molecule L1 influences proliferation and differentiation of neural precursor
cells. Substrate-coated L1 reduced proliferation of precursor cells in a
dose-dependent manner and increased neuronal and decreased astrocytic
differentiation when compared with poly-L-lysine or laminin
substrates. Enhancement of neuronal differentiation was more effective if L1
was offered via the cell surface of transfected fibroblasts compared with
substrate-coated purified L1. Furthermore, L1 decreased cholinergic-subtype
differentiation and accelerated GABAergic differentiation of precursor
cell-derived neurons in comparison with poly-L-lysine or laminin.
Generation of dopaminergic neurons was not influenced by L1. Experiments with
precursor cells generated from L1-deficient mice indicate that L1 acts via
heterophilic interaction on proliferation and differentiation of L1-negative
precursor cells and via a homophilic or L1 coreceptor-mediated interaction on
maturation of precursor cell-derived L1-positive neurons. Clonal analysis
revealed that L1 equally inhibits proliferation of monopotential, bipotential,
and multipotential precursor cells, but selectively enhances neuronal
differentiation of multipotential and bipotential neuron-astrocyte precursors.
Our observations support a new role for L1 or L1 ligands in neural precursor
cell proliferation and differentiation.
Key words: acetylcholine; adrenalin; cell adhesion molecules; differentiation; dopamine; GABA; L1; neural stem cells; proliferation
Received Apr. 7, 2003;
revised May. 27, 2003;
accepted May. 30, 2003.
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