Temporal Changes in Transcription Factor Expression Associated with the Differentiation State of Cerebellar Neural Stem/Progenitor Cells During Development

Abstract

During central nervous development, multi-potent neural stem/progenitor cells located in the ventricular/subventricular zones are temporally regulated to mostly produce neurons during early developmental stages and to produce glia during later developmental stages. After birth, the rodent cerebellum undergoes further dramatic development. It is also known that neural stem/progenitor cells are present in the white matter (WM) of the postnatal cerebellum until around P10, although the fate of these cells has yet to be determined. In the present study, it was revealed that primary neurospheres generated from cerebellar neural stem/progenitor cells at postnatal day 3 (P3) mainly differentiated into astrocytes and oligodendrocytes. In contrast, primary neurospheres generated from cerebellar neural stem/progenitor cells at P8 almost exclusively differentiated into astrocytes, but not oligodendrocytes. These results suggest that the differentiation potential of primary neurospheres changes depending on the timing of neural stem/progenitor cell isolation from the cerebellum. To identify the candidate transcription factors involved in regulating this temporal change, we utilized DNA microarray analysis to compare global gene-expression profiles of primary neurospheres generated from neural stem/progenitor cells isolated from either P3 or P8 cerebellum. The expression of zfp711, zfp618, barx1 and hoxb3 was higher in neurospheres generated from P3 cerebellum than from P8 by real-time quantitative PCR. Several precursor cells were found to express zfp618, barx1 or hoxb3 in the WM of the cerebellum at P3, but these transcription factors were absent from the WM of the P8 cerebellum.

Keywords: Cerebellum; DNA microarray; Neural stem/progenitor cells; Oligodendrocytes.