Pax6, Tbr2, and Tbr1 are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex.
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.
Englund
Chris
C
Department of Pathology, University of Washington, Seattle, Washington 98195-7470, USA.
Fink
Andy
A
Lau
Charmaine
C
Pham
Diane
D
Daza
Ray A M
RA
Bulfone
Alessandro
A
Kowalczyk
Tom
T
Hevner
Robert F
RF
D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005136:Eye Proteins / Q000096:biosynthesis; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000096:biosynthesis; D051379:Mice; D008938:Mitosis; D019579:Neocortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins / Q000096:biosynthesis; D013234:Stem Cells / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000096:biosynthesis; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis*
D004268:DNA-Binding Proteins; C491198:Eomes protein, mouse; D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D020825:T-Box Domain Proteins; C492271:Tbr1 protein, mouse; D014157:Transcription Factors