Neural precursor cell chain migration and division are regulated through different beta1 integrins.
Proliferation and tangential migration of neural precursor cells are essential determinants of CNS development. We have established cell culture models of both these processes using neural precursor cells grown as neurospheres. The pattern of migration that we observe in these cells is homotypic and occurs in the absence of a glial or neuronal scaffold, and is therefore equivalent to that previously described as chain migration. To determine the role of integrins in proliferation and migration, we have analysed the expression pattern of integrins on neurosphere cells and then performed blocking peptide and antibody experiments. Neurosphere cells express five major integrins, alpha5 beta1, alpha 6Abeta1, alphav beta1, alphav beta5 and alpha vbeta8 and, in addition, express low levels of alpha 6Bbeta1. Chain migration is inhibited by blocking the alpha 6beta1 integrin. Proliferation, by contrast, is inhibited by blocking the other beta1 integrins, alphav beta1 and alpha5 beta1. These results show that integrins are important regulators of neural precursor cell behaviour, with distinct beta1 integrins regulating proliferation and migration. They also demonstrate a novel role for the alpha6 beta1 integrin in the cell-cell interactions underlying homotypic chain migration.
Wellcome/CRC Institute of Developmental Biology and Cancer, Tennis Court Road, Cambridge, CB2 1QR and Department of Medical Genetics, University of Cambridge, Cambridge, UK.
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TS
Jacques
J B
JB
Relvas
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Nishimura
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Pytela
G M
GM
Edwards
C H
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Streuli
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ffrench-Constant
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016590:Aphidicolin / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000254:growth & development*; D005353:Fibronectins / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D019012:Integrin beta1 / Q000145:classification / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000032:analysis; D051381:Rats; D013234:Stem Cells / Q000378:metabolism*; D019063:Tenascin / Q000494:pharmacology; D014404:Tubulin / Q000032:analysis
D000911:Antibodies, Monoclonal; D005353:Fibronectins; D005904:Glial Fibrillary Acidic Protein; D019012:Integrin beta1; D009419:Nerve Tissue Proteins; D019063:Tenascin; D014404:Tubulin; D016590:Aphidicolin