Developmental regulation of alphav integrins produces functional changes in astrocyte behavior.
To examine the role of the extracellular matrix in regulating astrocyte behavior we previously characterized alphav integrin expression on postnatal astrocytes in vitro and found that they express alphavbeta5 and alphavbeta8. Here we show that differentiation of immature cells into astrocytes is accompanied by developmental regulation of alphav integrins, downregulation of alphavbeta1 and alphavbeta8, and upregulation of alphavbeta5. In addition, using two previously described astrocyte cell lines, we found that the neurite-permissive A7 cell line expressed high levels of alphavbeta1 in addition to alphavbeta5 and alphavbeta8, while the neurite-inhibitory Neu7 cell line expressed only alphavbeta5. To examine integrin function we generated clones of the Neu7 cell line expressing alphavbeta1 or alphavbeta3 in addition to alphavbeta5. This showed that the parent Neu7 cells migrated more slowly than the A7 cells on fibronectin and vitronectin, but that Neu7 cells expressing alphavbeta1 or alphavbeta3 integrins showed enhanced migration on fibronectin and vitronectin, respectively. These results show that alphav integrin expression is regulated during astrocyte development and confirm an instructive role in cell migration for alphavbeta1 in embryonic cells and alphavbeta3 in astroglial tumors.
Milner
R
R
Department of Medical Genetics, Department of Physiology, University of Cambridge and Cambridge Centre for Brain Repair, University Forvie Site, Robinson Way, Cambridge, CB2 2PT, United Kingdom. rmilner@scripps.edu
Relvas
J B
JB
Fawcett
J
J
ffrench-Constant
C
C
D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D001253:Astrocytes / Q000166:cytology* / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D005353:Fibronectins / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D039564:Integrin alphaV; D007365:Intercellular Junctions; D051381:Rats; D014162:Transfection; D019096:Vitronectin / Q000494:pharmacology
D015703:Antigens, CD; D005353:Fibronectins; D039564:Integrin alphaV; D019096:Vitronectin