Transcription Mapping of Embryonic Rat Brain Reveals EGR-1 Induction in SOX2 Neural Progenitor Cells

• Published in: Frontiers in molecular neuroscience 2011-01, Vol.4, p.6-6
• Main Authors: Wells, Timothy, Rough, Kirsty, Carter, David A
• Format: Article
• Language: English
• Subjects: Antigens; Binding sites; Brain; Brain mapping; Clonal deletion; Conserved sequence; Doublecortin protein; EGR-1; EGR-1 protein; Embryogenesis; Epigenetics; Fetuses; Gene expression; Green fluorescent protein; Growth factors; Kinases; Laboratories; Localization; Neostriatum; Nestin; neural progenitor cells; Neural stem cells; Neuroblastoma; Neuroscience; Nuclear receptors; Nurr1 protein; Phenotypes; Progenitor cells; Proteins; Regulatory sequences; SOX2; transcription factor; Transcription factors; transgenic; Vimentin
• ISSN: 1662-5099; 1662-5099
• DOI: 10.3389/fnmol.2011.00006

Neuronal expression of the early growth response-1 (EGR-1; NGFI-A/Zif268) transcription factor has been extensively studied in the adult mammalian brain and linked to aspects of mature physiological/behavioral function. In contrast, this factor has not been studied in detail in the embryonic brain. Here, we used a fluorescent protein-encoding Egr-1 transgene to map the cellular distribution of Egr-1 transcription in embryonic rat brain. We identified a novel, widely distributed population of GFP(+) cells, characterized as a precursor/stem cell phenotype by co-localization with SOX2/nestin/vimentin/S-100β and exclusion from other known cellular markers including DCX/BLBP/TBR2/NURR1. At both E18 and E20, these cells were located across the developing brain but concentrated in the subplate and intermediate zones. The transgene was also highly expressed in developing (NeuN(+)) striatal neurons. The authentic expression pattern that we observed for the rEgr-1 transgene sequence indicates that restriction to neuronal/precursor cells is largely driven by proximal 5(') sequence. Deletion of conserved Egr-1 silencer (neuron restrictive silencer factor) elements did not markedly alter transcriptional activity in transfected cells; this is consistent with a dominant role for positive factors in the control of cell-specific Egr-1 expression. Induction of Egr-1 in a population of SOX2(+) cells indicates a co-incidence of extrinsic (EGR-1) and cell-intrinsic (SOX2) cellular signals that may form a novel level of progenitor cell regulation. The wide distribution of EGR-1 signaling in SOX2(+) cells suggests an organizational role during late embryonic brain development.