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 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.
Shimazaki
T
T
Department of Cell Biology and Anatomy, University of Calgary Faculty of Medicine, 3330 Hospital Drive N.W., Calgary, AB, Canada T2N 4N1.
Arsenijevic
Y
Y
Ryan
A K
AK
Rosenfeld
M G
MG
Weiss
S
S
D000818:Animals; D001483:Base Sequence; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D003342:Corpus Striatum / Q000166:cytology* / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D016373:DNA, Antisense / Q000235:genetics / Q000494:pharmacology; D004268:DNA-Binding Proteins; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D051379:Mice; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D050809:POU Domain Factors; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D017931:DNA Primers; D016373:DNA, Antisense; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D050809:POU Domain Factors; D014157:Transcription Factors; C074067:Pou3f4 protein, mouse; D007334:Insulin-Like Growth Factor I