Pax6, Tbr2, and Tbr1 Are Expressed Sequentially by Radial Glia, Intermediate Progenitor Cells, and Postmitotic Neurons in Developing Neocortex

By Chris Englund, Andy Fink, C. Lau, D. Pham, R. Daza, A. Bulfone, Tom Kowalczyk, R. Hevner. 2005

1,295 citations recorded by the source corpus.

The developing neocortex contains two types of progenitor cells for glutamatergic, pyramidal-projection neurons. The first type, radial glia, produce neurons and glia, divide at the ventricular surface, and express Pax6, a homeodomain transcription factor. The second type, intermediate progenitor cells, are derived from radial glia, produce only neurons, and divide away from the ventricular surface. Here we show that the transition from radial glia to intermediate progenitor cell is associated with upregulation of Tbr2, a T-domain transcription factor, and downregulation of Pax6. Accordingly, Tbr2 expression in progenitor compartments (the subventricular zone and ventricular zone) rises and falls with cortical plate neurogenesis. The subsequent transition from intermediate progenitor cell to postmitotic neuron is marked by downregulation of Tbr2 and upregulation of Tbr1, another T-domain transcription factor. These findings delineate the transcription factor sequence Pax6 → Tbr2 → Tbr1 in the differentiation of radial glia → intermediate progenitor cell → postmitotic projection neuron. This transcription factor sequence is modified in preplate neurons, in which Tbr2 is transiently coexpressed with Tbr1, and in the direct differentiation pathway from radial glia → postmitotic projection neuron, in which Tbr2 is expressed briefly or not at all.

Subfields: Cancer Research, Developmental Neuroscience, Molecular Biology

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Citations in the corpus

A role for intermediate radial glia in the tangential expansion of the mammalian cerebral cortex. (2011, methodology): “…a variety of combinations of different transcription factors including Pax6, Tbr2, Sox2, and Olig2, whereas in the mouse SVZ virtually all progenitors express Tbr2 and not Pax6 (Englund et al. 2005; Zecevic et al. 2005; Howard et al. 2006; Mo et al. 2007; Mo and Zecevic 2008; Hansen et al. 2010).”
The germinal matrices in the developing dentate gyrus are composed of neuronal progenitors at distinct differentiation stages (2013, background): “This gradation likely indicates transition of GC differentiating stages, suggesting conservation of sequential expression of these neurogenic TFs. Based on the sequential TFs cascade (Englund et al., 2005; Hevner et al., 2006), the differentiation process of the GCs is suggested as described below.”
Neural progenitors, neurogenesis and the evolution of the neocortex (2014, background): “3). bIPs downregulate astroglial markers and, on their way to the SVZ, start expressing the transcription factor Tbr2 (also known as Eomes) (Englund et al., 2005; Cappello et al., 2006). bIPs can divide in a self-consuming fashion, undergoing (like aIPs) one round of symmetric neurogenic division (H”
The genetic architecture of the human cerebral cortex (2020, background): “4 × 10) is of interest because of its proximity (~200 kb) to EOMES (also known as TBR2), which is expressed specifically in intermediate progenitor cells in the developing fetal cortex (35).”
Temporal Control of Mammalian Cortical Neurogenesis by m6A Methylation (2017, neutral): “Neurogenic Pax6+ RGCs give rise to intermediate progenitor cells (IPCs) expressing Tbr2/ Eomes (Englund et al., 2005).”
Development and Evolution of the Human Neocortex (2011, positive): “This partially reconciled the earlier observations of GFAP and non-GFAP expressing progenitor cells in the VZ because, at early stages prior to formation of a distinct SVZ, intermediate progenitor (IP) cells also divide in the VZ (Englund et al., 2005; Noctor et al., 2008; Kowalczyk et al., 2009).”
The maternal interleukin-17a pathway in mice promotes autismlike phenotypes in offspring (2016, background): “Co nt an tiIL -1 7a PBS Poly(I:C) Co nt an tiIL -1 7a 0 500 1000 1500 2000 To ta l d is ta nc e m ov ed ( cm ) 2500 0 100 200 300 400 U S V in de x Co nt an ti- IL -1 7a PBS Poly(I:C) **** ** Co nt an ti- IL -1 7a 0 20 40 60 80 % In te ra ct io n 100 Social Inanimate ** * ** Co nt an ti- IL -1 7a PB”
Developmental cell biology: The cell biology of neurogenesis (2005, background): “65 ) and the genes that encode the transcription factors TBR2 (Ref”
bigSCale: an analytical framework for big-scale single-cell data (2017, background): “Similarly, bigSCale captured the hallmarks of the main stages of the neuronal lineage (Englund et al. 2005), indicated by the expression of Pax6 (radial glia), Eomes (TBR2, committed progenitors), andTbr1 (differentiated neurons) (Fig.”
Multiple knockout mouse models reveal lincRNAs are required for life and brain development (2013, methodology): “Embryonic brains, dissected in cold PBS and fixed in 4% PFA/PBS overnight at 4°C, and P7 brains dissected from pups transcardially perfused with 4% PFA and post-fixed as described above, were processed for Nissl staining and immunofluorescence as previously described (Englund et al., 2005; Molyneaux”
Self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals. (2008, background): “and occupy the cortical subventricular zone (Figure S6J; Englund et al., 2005 ).”