TY - JOUR
T1 - Differential expression levels of Sox9 in early neocortical radial glial cells regulate the decision between stem cell maintenance and differentiation
AU - Fabra-Beser, Jaime
AU - de Araujo, Jessica Alves Medeiros
AU - Marques-Coelho, Diego
AU - Goff, Loyal A.
AU - Costa, Marcos R.
AU - Müller, Ulrich
AU - Gil-Sanz, Cristina
N1 - Funding Information:
This work was supported by the Spanish Ministry of Science and Innovation (Grant SAF-2017-82880-R to C.G.-S.) and National Institutes of Health (Grant RF1-MH-121539 to U.M.). C.G.-S. received a Ramón y Cajal Grant from the Spanish Ministry of Science and Innovation (RyC-2015-19058). J.A.M.d.A. and D.M.-C. were supported in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Grant BEX: 717115-3). U.M. is a Bloomberg Distinguished Professor for Neuroscience and Biology, Johns Hopkins School of Medicine. We thank members of the laboratory for comments and criticism; Isabel Fariñas and Sacramento R. Ferrón for critical comments, reagents, and sharing of equipment. We also thank Cristina Andrés Carbonell for assistance with mouse maintenance. The authors declare no competing financial interests. Correspondence should be addressed to Cristina Gil-Sanz at cristina.gil@uv.es. https://doi.org/10.1523/JNEUROSCI.2905-20.2021 Copyright © 2021 Fabra-Beser et al.
Publisher Copyright:
Copyright © 2021 Fabra-Beser et al.
PY - 2021/8/18
Y1 - 2021/8/18
N2 - Radial glial progenitor cells (RGCs) in the dorsal telencephalon directly or indirectly produce excitatory projection neurons and macroglia of the neocortex. Recent evidence shows that the pool of RGCs is more heterogeneous than originally thought and that progenitor subpopulations can generate particular neuronal cell types. Using single-cell RNA sequencing, we have studied gene expression patterns of RGCs with different neurogenic behavior at early stages of cortical development. At this early age, some RGCs rapidly produce postmitotic neurons, whereas others self-renew and undergo neurogenic divisions at a later age. We have identified candidate genes that are differentially expressed among these early RGC subpopulations, including the transcription factor Sox9. Using in utero electroporation in embryonic mice of either sex, we demonstrate that elevated Sox9 expression in progenitors affects RGC cell cycle duration and leads to the generation of upper layer cortical neurons. Our data thus reveal molecular differences between progenitor cells with different neurogenic behavior at early stages of corticogenesis and indicates that Sox9 is critical for the maintenance of RGCs to regulate the generation of upper layer neurons.
AB - Radial glial progenitor cells (RGCs) in the dorsal telencephalon directly or indirectly produce excitatory projection neurons and macroglia of the neocortex. Recent evidence shows that the pool of RGCs is more heterogeneous than originally thought and that progenitor subpopulations can generate particular neuronal cell types. Using single-cell RNA sequencing, we have studied gene expression patterns of RGCs with different neurogenic behavior at early stages of cortical development. At this early age, some RGCs rapidly produce postmitotic neurons, whereas others self-renew and undergo neurogenic divisions at a later age. We have identified candidate genes that are differentially expressed among these early RGC subpopulations, including the transcription factor Sox9. Using in utero electroporation in embryonic mice of either sex, we demonstrate that elevated Sox9 expression in progenitors affects RGC cell cycle duration and leads to the generation of upper layer cortical neurons. Our data thus reveal molecular differences between progenitor cells with different neurogenic behavior at early stages of corticogenesis and indicates that Sox9 is critical for the maintenance of RGCs to regulate the generation of upper layer neurons.
KW - Cortical development
KW - Progenitors diversity
KW - Radial glia cells
KW - Sox9
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U2 - 10.1523/JNEUROSCI.2905-20.2021
DO - 10.1523/JNEUROSCI.2905-20.2021
M3 - Article
C2 - 34266896
AN - SCOPUS:85113853881
SN - 0270-6474
VL - 41
SP - 6969
EP - 6986
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 33
ER -