Abstract
BackgroundDuring corticogenesis, genetic programs encoded in progenitor cells at different developmental stages and inherited in postmitotic neurons specify distinct layer and area identities. Transcription factor Zbtb20 has been shown to play a role for hippocampal development but whether it is implicated in mammalian neocortical morphogenesis remains unknown.ResultsHere, we report that during embyogenesis transcription factor Zbtb20 has a dynamic spatio-temporal expression pattern in mitotic cortical progenitors through which it modulates the sequential generation of cortical neuronal layer identities. Zbtb20 knock out mice exhibited enhanced populations of early born L6-L4 neuronal subtypes and a dramatic reduction of the late born L3/L2 neurons. This defect was due to a temporal misbalance in the production of earlier versus later born neurons, leading to a progressive diminishing of the progenitor pool for the generation of L3-L2 neurons. Zbtb20 implements these temporal effects in part by binding to promoter of the orphan nuclear receptor CoupTF1/Nr2f1. In addition to its effects exerted in cortical progenitors, the postmitotic expression of Zbtb20 in L3/L2 neurons starting at birth may contribute to their proper differentiation and migration.ConclusionsOur findings reveal Zbtb20 as a novel temporal regulator for the generation of layer-specific neuronal identities.Electronic supplementary materialThe online version of this article (doi:10.1186/s13041-016-0242-2) contains supplementary material, which is available to authorized users.
Highlights
During corticogenesis, genetic programs encoded in progenitor cells at different developmental stages and inherited in postmitotic neurons specify distinct layer and area identities
Dynamic Zbtb20 expression in telencephalic progenitors By E11.5 a gradient of Zbtb20-lacZ activity was evident in the ventricular zone (VZ) of the lateral pallium (LP) of the heterozygous Zbtb20lacZ/+ embryos (Additional file 1: Figure S1A, arrow)
Co-staining for Zbtb20, radial glial cells (RGCs) marker Pax6 and the mitotic marker phosphorylated vimentin confirmed that transcription factor (TF) Zbtb20 is expressed in dividing RGCs at the apical surface of VZ (Fig. 1e1e4, arrows; 90 out of 93 assayed pVim+ cells on the apical surface were co-labeled for Zbtb20, 97 %, n = 3)
Summary
Genetic programs encoded in progenitor cells at different developmental stages and inherited in postmitotic neurons specify distinct layer and area identities. Generation of neuronal sets with a layer-specific identity depends on an intrinsically encoded genetic program and environmental cues acting during the S-phase of the mitotic cycle [1]. Increasing recent evidence support the view that the precise temporal programs for production of LL and UL neuronal fates relies on intrinsic mechanisms in early and late progenitors, respectively, characterized by specific combinatorial expression of TFs at distinct developmental time points [7,8,9,10,11,12,13]. Suppression of the expression of Foxg at E10.5 is required to make a switch from generation of reelin-positive Cajal-Retzius
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