FOXP1 orchestrates neurogenesis in human cortical basal radial glial cells.
FOXP1 orchestrates neurogenesis in human cortical basal radial glial cells.
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DOI：
10.1371/journal.pbio.3001852
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发表时间：
2023-08
期刊：
影响因子：
9.8
通讯作者：
Konopka, Genevieve
中科院分区：
文献类型：
--
作者：
Park, Seon Hye E.;Kulkarni, Ashwinikumar;Konopka, Genevieve
During cortical development, human basal radial glial cells (bRGCs) are highly capable of sustained self-renewal and neurogenesis. Selective pressures on this cell type may have contributed to the evolution of the human neocortex, leading to an increase in cortical size. bRGCs have enriched expression for Forkhead Box P1 (FOXP1), a transcription factor implicated in neurodevelopmental disorders (NDDs) such as autism spectrum disorder. However, the cell type–specific roles of FOXP1 in bRGCs during cortical development remain unexplored. Here, we examine the requirement for FOXP1 gene expression regulation underlying the production of bRGCs using human brain organoids. We examine a developmental time point when FOXP1 expression is highest in the cortical progenitors, and the bRGCs, in particular, begin to actively produce neurons. With the loss of FOXP1, we show a reduction in the number of bRGCs, as well as reduced proliferation and differentiation of the remaining bRGCs, all of which lead to reduced numbers of excitatory cortical neurons over time. Using single-nuclei RNA sequencing and cell trajectory analysis, we uncover a role for FOXP1 in directing cortical progenitor proliferation and differentiation by regulating key signaling pathways related to neurogenesis and NDDs. Together, these results demonstrate that FOXP1 regulates human-specific features in early cortical development. During cortical development, human basal radial glial cells show sustained self-renewal and neurogenesis. This study uses a human brain organoid system and snRNA-seq to reveal the the importance of role of FOXP1, an autism-relevant transcription factor, in regulating radial glial cell function and cortical development.
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DOI：
10.1002/wdev.375
发表时间：
2020-09
期刊：
Wiley interdisciplinary reviews. Developmental biology
影响因子：
--
作者：
Co M;Anderson AG;Konopka G
通讯作者：
Konopka G
影响因子：
64.8
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
影响因子：
4
作者：
Dennis MY;Eichler EE
通讯作者：
Eichler EE
影响因子：
23.9
作者：
Bershteyn M;Nowakowski TJ;Pollen AA;Di Lullo E;Nene A;Wynshaw-Boris A;Kriegstein AR
通讯作者：
Kriegstein AR