期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 282, 期 12, 页码 9172-9181出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M608067200
关键词
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Tenascin C (Tnc) is an alternatively spliced, multimodular extracellular matrix glycoprotein present in the ventricular zone of the developing brain. Pax6-deficient small eye (sey) mouse mutants show an altered Tnc expression pattern. Here, we investigated the expression of Tnc isoforms in neural stem/progenitor cells and their regulation by the paired-box transcription factor Pax6. Neural stem/progenitor cells cultured as neurospheres strongly expressed Tnc on the protein level. The Tnc isoform expression in neural stem/progenitor cells was analyzed by reverse transcriptase-PCR and dot blot Southern hybridization: In total, 20 different Tnc isoforms were detected in neurospheres derived from embryonic forebrain cell suspensions. The Tnc isoform containing the fibronectin type III domains A1A4BD is novel and might be neural stem/progenitor cell-specific. Transient overexpression of Pax6 in neurospheres of the medial ganglionic eminence did not alter the total Tnc mRNA expression level but showed a pronounced regulative effect on different Tnc isoforms. The larger Tnc isoforms containing four, five, and six additional alternatively spliced fibronectin type III domains were up-regulated, whereas the small Tnc isoforms without any or with one additional domain were down-regulated. Thus, Pax6 is a homeodomain protein that also modulates the splicing machinery. We conclude that the combinatorial code of Tnc isoform expression in the neural stem/progenitor cell is complex and regulated by Pax6. These findings suggest a functional significance for individual Tnc isoforms in neural stem/progenitor cells.
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