A role for the POU-III transcription factor Brn-4 in the regulation of striatal neuron precursor differentiation

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 β‐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 β‐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.