Gene expression changes in the course of neural progenitor cell differentiation.
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.
Gurok
Ulf
U
Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
Steinhoff
Christine
C
Lipkowitz
Bettina
B
Ropers
H-Hilger
HH
Scharff
Constance
C
Nuber
Ulrike A
UA
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D002455:Cell Division; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D020547:Lateral Ventricles / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000166:cytology*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D018874:Spheroids, Cellular / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C073922:neurotrophin 4