TY - JOUR

T1 - Beta1 integrins activate a MAPK signalling pathway in neural stem cells that contributes to their maintenance.

AU - Campos, Lia S

AU - Leone, Dino P

AU - Relvas, Joao B

AU - Brakebusch, Cord

AU - Fässler, Reinhard

AU - Suter, Ueli

AU - ffrench-Constant, Charles

N1 - Keywords: Animals; Antigens, CD29; Blotting, Western; Bromodeoxyuridine; Cell Culture Techniques; Cell Separation; Cells, Cultured; Coloring Agents; Epithelial Cells; Epithelium; Extracellular Matrix; Fibronectins; Flow Cytometry; Immunohistochemistry; Laminin; MAP Kinase Signaling System; Mice; Mice, Knockout; Models, Biological; Neurons; Phosphorylation; Signal Transduction; Stem Cells; Time Factors

PY - 2004

Y1 - 2004

N2 - The emerging evidence that stem cells develop in specialised niches highlights the potential role of environmental factors in their regulation. Here we examine the role of beta1 integrin/extracellular matrix interactions in neural stem cells. We find high levels of beta1 integrin expression in the stem-cell containing regions of the embryonic CNS, with associated expression of the laminin alpha2 chain. Expression levels of laminin alpha2 are reduced in the postnatal CNS, but a population of cells expressing high levels of beta1 remains. Using neurospheres - aggregate cultures, derived from single stem cells, that have a three-dimensional architecture that results in the localisation of the stem cell population around the edge of the sphere - we show directly that beta1 integrins are expressed at high levels on neural stem cells and can be used for their selection. MAPK, but not PI3K, signalling is required for neural stem cell maintenance, as assessed by neurosphere formation, and inhibition or genetic ablation of beta1 integrin using cre/lox technology reduces the level of MAPK activity. We conclude that integrins are therefore an important part of the signalling mechanisms that control neural stem cell behaviour in specific areas of the CNS.

AB - The emerging evidence that stem cells develop in specialised niches highlights the potential role of environmental factors in their regulation. Here we examine the role of beta1 integrin/extracellular matrix interactions in neural stem cells. We find high levels of beta1 integrin expression in the stem-cell containing regions of the embryonic CNS, with associated expression of the laminin alpha2 chain. Expression levels of laminin alpha2 are reduced in the postnatal CNS, but a population of cells expressing high levels of beta1 remains. Using neurospheres - aggregate cultures, derived from single stem cells, that have a three-dimensional architecture that results in the localisation of the stem cell population around the edge of the sphere - we show directly that beta1 integrins are expressed at high levels on neural stem cells and can be used for their selection. MAPK, but not PI3K, signalling is required for neural stem cell maintenance, as assessed by neurosphere formation, and inhibition or genetic ablation of beta1 integrin using cre/lox technology reduces the level of MAPK activity. We conclude that integrins are therefore an important part of the signalling mechanisms that control neural stem cell behaviour in specific areas of the CNS.

U2 - 10.1242/dev.01199

DO - 10.1242/dev.01199

M3 - Journal article

C2 - 15226259

VL - 131

SP - 3433

EP - 3444

JO - Development

JF - Development

SN - 0950-1991

IS - 14

ER -