Abstract
An important feature of the cerebral cortex is its layered organization, which is modulated in an area-specific manner. We found that the transcription factor AP2γ regulates laminar fate in a region-specific manner. Deletion of AP2γ (also known as Tcfap2c) during development resulted in a specific reduction of upper layer neurons in the occipital cortex, leading to impaired function and enhanced plasticity of the adult visual cortex. AP2γ functions in apical progenitors, and its absence resulted in mis-specification of basal progenitors in the occipital cortex at the time at which upper layer neurons were generated. AP2γ directly regulated the basal progenitor fate determinants Math3 (also known as Neurod4) and Tbr2, and its overexpression promoted the generation of layer II/III neurons in a time- and region-specific manner. Thus, AP2γ acts as a regulator of basal progenitor fate, linking regional and laminar specification in the mouse developing cerebral cortex.
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Change history
25 September 2009
In the version of this article initially published, one of the corresponding authors’ email addresses was misspelled. It should be luisapinto@ecsaude.uminho.pt. In addition, errors occurred in some of the numbers listed in the last subsection of the Results section. Instead of “Notably, AP2γ−/− mice also showed alterations in cortical binocularity (Fig. 7c,d and Supplementary Table 2) and a tendency toward an increased latency of visual response (wild type = 109.95 ms, AP2γ/− = 127.19 ms; Supplementary Table 2). […] Indeed, monocular deprivation for 3 d caused a significant change in binocularity in adult AP2γ−/− (P = 0.027), but not wild-type (P = 0.365), mice (Fig. 7d),” the affected sentences should read, “Notably, AP2γ−/− mice also showed alterations in cortical binocularity (Fig. 7c,d and Supplementary Table 2) and a tendency toward an increased latency of visual response (wild type = 110.0 ± 3.8 ms, AP2γ−/− = 127.2 ± 6.4 ms; t-test, P = 0.05; Supplementary Table 2). […] Indeed, monocular deprivation for 3 d caused a significant change in binocularity in adult AP2γ−/− (P = 0.01), but not wild-type (P = 0.365), mice (Fig. 7d).” The errors have been corrected in the HTML and PDF versions of the article.
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Acknowledgements
We are very grateful to M. Moser, S. Pfaff, C. Schuurmans and Y. Gotoh for in situ probes and to R. Jäger for providing reagents. We thank T. Öztürk, A. Steiner, A. Waiser and D. Franzen for excellent technical assistance. H.S. was supported by the Deutsche Forschungsgemeinschaft. M.G. was supported by the Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung and the Bavarian government. L.P. is supported by the Portuguese Fundaçäo para a Ciência e Tecnologia/European Social Fund.
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L.P. did most of the experimental work. D.D. contributed to the in vitro studies and to immunostaining in the embryonic cortex. M.-T.S. contributed to the in utero injections. J.N. contributed to the luciferase assay. M.I. and J.B. conducted the microarrays analyses. M.S.B. contributed to the beads injections. L.R., L.G., C.C. and M.C. conducted the visual functional analysis. S.N.W. and H.S. generated the AP2γ conditional knockout mice. V.T. contributed with antibodies. K.B. conducted the adult human analysis. F.G. prepared the Mash1 construct and provided the Ngn2KiMash1 mice. N.Z. conducted the embryonic human analyses. C.D. conducted the embryonic monkey analyses. M.G. supervised the project and wrote the manuscript together with L.P.
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Pinto, L., Drechsel, D., Schmid, MT. et al. AP2γ regulates basal progenitor fate in a region- and layer-specific manner in the developing cortex. Nat Neurosci 12, 1229–1237 (2009). https://doi.org/10.1038/nn.2399
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DOI: https://doi.org/10.1038/nn.2399
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