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The Journal of Neuroscience, June 30, 2004, 24(26):5982-6002; doi:10.1523/JNEUROSCI.0809-04.2004

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Cellular/Molecular
Gene Expression Changes in the Course of Neural Progenitor Cell Differentiation

Ulf Gurok,^1,2 Christine Steinhoff,¹ Bettina Lipkowitz,¹ H.-Hilger Ropers,¹ Constance Scharff,¹ and Ulrike A. Nuber¹

¹Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany, and ²Freie Universität Berlin, Fachbereich Biologie, Chemie, Pharmazie, 14195 Berlin, Germany

The molecular changes underlying neural progenitor differentiation are essentially unknown. We applied cDNA microarrays with 13,627 clones to measure dynamic gene expression changes during the in vitro differentiation of neural progenitor cells that were isolated from the subventricular zone of postnatal day 7 mice and grown in vitro as neurospheres. In two experimental series in which we withdrew epidermal growth factor and added the neurotrophins Neurotrophin-4 or BDNF, four time points were investigated: undifferentiated cells grown as neurospheres, and cells 24, 48, and 96 hr after differentiation. Expression changes of selected genes were confirmed by semiquantitative RT-PCR. Ten different groups of gene expression dynamics obtained by cluster analysis are described. To correlate selected gene expression changes to the localization of respective proteins, we performed immunostainings of cultured neurospheres and of brain sections from adult mice. Our results provide new insights into the genetic program of neural progenitor differentiation and give strong hints to as yet unknown cellular communications within the adult subventricular zone stem cell niche.

Key words: development; differentiation; hybridization; ventricle; stem cell; microarray; subventricular zone; rostral migratory stream; neurosphere

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Received Dec 2, 2003; revised April 26, 2004; accepted May 14, 2004.

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