Siegenthaler Julie A, Tremper-Wells Barbara A, Miller Michael W
Department of Neuroscience and Physiology, State University of New York-Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA.
Cereb Cortex. 2008 Aug;18(8):1865-75. doi: 10.1093/cercor/bhm209. Epub 2007 Dec 7.
Foxg1 is a transcription factor that is critical for forebrain development. Foxg1(+/Cre) mice were used to test the hypotheses 1) that the subventricular zone (SZ) generates supragranular neurons, 2) that Foxg1-regulated activities define the output from the SZ, and 3) that Foxg1 is involved in the suppression of p21-initiated cell-cycle exit. Foxg1(+/Cre) mice have thinner neocortices than wild-type controls, specifically in the supragranular layers, as detected by Brn2 immunostaining. Cell proliferation in the ventricular zone (VZ) and SZ was examined to investigate the reduction in upper layer neurons. The number of cycling VZ cells was similar in Foxg1(+/+) and Foxg1(+/Cre) brains. Interestingly, cell proliferation in the SZ and intermediate progenitor cell (IPC) production (noted by Tbr2-immunostaining) was reduced in Foxg1(+/Cre) brains. These decreases coincided with increased expression of the cell-cycle inhibitor p21 in the VZ and SZ. Furthermore, colocalization of p21 with markers of cell proliferation and IPCs indicated that p21 was temporally expressed to influence the proliferative fate of IPCs. Thus, the present data are consistent with the above hypotheses, particularly, that during corticogenesis, Foxg1-regulated activities enable the expansion of the IPC population likely through suppression of p21-dependent cell-cycle exit.
Foxg1是一种对前脑发育至关重要的转录因子。利用Foxg1(+/Cre)小鼠来验证以下假设：1) 室下区（SZ）产生颗粒上层神经元；2) Foxg1调控的活动决定了SZ的输出；3) Foxg1参与抑制p21引发的细胞周期退出。通过Brn2免疫染色检测发现，Foxg1(+/Cre)小鼠的新皮质比野生型对照更薄，特别是在颗粒上层。检测室管膜区（VZ）和SZ的细胞增殖情况，以研究上层神经元数量减少的原因。在Foxg1(+/+)和Foxg1(+/Cre)小鼠的大脑中，处于细胞周期的VZ细胞数量相似。有趣的是，Foxg1(+/Cre)小鼠大脑中SZ的细胞增殖和中间祖细胞（IPC）产生（通过Tbr2免疫染色标记）减少。这些减少与VZ和SZ中细胞周期抑制剂p21表达的增加相一致。此外，p21与细胞增殖和IPC标志物的共定位表明，p21在特定时间表达，以影响IPC的增殖命运。因此，目前的数据与上述假设一致，特别是在皮质发生过程中，Foxg1调控的活动可能通过抑制p21依赖的细胞周期退出，使IPC群体得以扩增。
