TY - JOUR

T1 - Regulation of neural progenitor proliferation and survival by beta1 integrins.

AU - Leone, Dino P

AU - Relvas, João B

AU - Campos, Lia S

AU - Hemmi, Silvio

AU - Brakebusch, Cord

AU - Fässler, Reinhard

AU - Ffrench-Constant, Charles

AU - Suter, Ueli

N1 - Keywords: Animals; Antigens, CD29; Cell Adhesion; Cell Death; Cell Movement; Cell Proliferation; Cell Survival; Cells, Cultured; Female; Fibronectins; Growth Substances; Intermediate Filament Proteins; Laminin; Male; Mice; Mice, Transgenic; Nerve Tissue Proteins; Neurons; Signal Transduction; Stem Cells

PY - 2005

Y1 - 2005

N2 - Neural stem cells give rise to undifferentiated nestin-positive progenitors that undergo extensive cell division before differentiating into neuronal and glial cells. The precise control of this process is likely to be, at least in part, controlled by instructive cues originating from the extracellular environment. Some of these cues are interpreted by the integrin family of extracellular matrix receptors. Using neurosphere cell cultures as a model system, we show that beta1-integrin signalling plays a crucial role in the regulation of progenitor cell proliferation, survival and migration. Following conditional genetic ablation of the beta1-integrin allele, and consequent loss of beta1-integrin cell surface protein, mutant nestin-positive progenitor cells proliferate less and die in higher numbers than their wild-type counterparts. Mutant progenitor cell migration on different ECM substrates is also impaired. These effects can be partially compensated by the addition of exogenous growth factors. Thus, beta1-integrin signalling and growth factor signalling tightly interact to control the number and migratory capacity of nestin-positive progenitor cells.

AB - Neural stem cells give rise to undifferentiated nestin-positive progenitors that undergo extensive cell division before differentiating into neuronal and glial cells. The precise control of this process is likely to be, at least in part, controlled by instructive cues originating from the extracellular environment. Some of these cues are interpreted by the integrin family of extracellular matrix receptors. Using neurosphere cell cultures as a model system, we show that beta1-integrin signalling plays a crucial role in the regulation of progenitor cell proliferation, survival and migration. Following conditional genetic ablation of the beta1-integrin allele, and consequent loss of beta1-integrin cell surface protein, mutant nestin-positive progenitor cells proliferate less and die in higher numbers than their wild-type counterparts. Mutant progenitor cell migration on different ECM substrates is also impaired. These effects can be partially compensated by the addition of exogenous growth factors. Thus, beta1-integrin signalling and growth factor signalling tightly interact to control the number and migratory capacity of nestin-positive progenitor cells.

U2 - 10.1242/jcs.02396

DO - 10.1242/jcs.02396

M3 - Journal article

C2 - 15928047

VL - 118

SP - 2589

EP - 2599

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - Pt 12

ER -