First Author | Shimazaki T | Year | 1999 |
Journal | EMBO J | Volume | 18 |
Issue | 2 | Pages | 444-56 |
PubMed ID | 9889200 | Mgi Jnum | J:52381 |
Mgi Id | MGI:1329221 | Doi | 10.1093/emboj/18.2.444 |
Citation | Shimazaki T, et al. (1999) A role for the POU-III transcription factor Brn-4 in the regulation of striatal neuron precursor differentiation. EMBO J 18(2):444-56 |
abstractText | Both insulin-like growth factor-I (IGF-I) and brain-derived neurotrophic factor (BDNF) induce the differentiation of post-mitotic neuronal precursors, derived from embryonic day 14 (E14) mouse striatal multipotent stem cells. Here we ask whether this differentiation is mediated by a member of the POU-III class of neural transcription factors. Exposure of stem cell progeny to either IGF-I or BDNF resulted in a rapid upregulation of Brn-4 mRNA and protein. Indirect immunocytochemistry with Brn-4 antiserum showed that the protein was expressed in newly generated neurons. Other POU-III genes, such as Brn-1 and Brn-2, did not exhibit this upregulation. Basic FGF, a mitogen for these neuronal precursors, did not stimulate Brn-4 expression. In the E14 mouse striatum, Brn-4-immunoreactive cells formed a boundary between the nestin-immunoreactive cells of the ventricular zone and the beta-tubulin-immunoreactive neurons migrating into the mantle zone. Loss of Brn-4 function during the differentiation of stem cell-derived or primary E14 striatal neuron precursors, by inclusion of antisense oligonucleotides, caused a reduction in the number of beta-tubulin-immunoreactive neurons. These findings suggest that Brn-4 mediates, at least in part, the actions of epigenetic signals that induce striatal neuron-precursor differentiation. |