Yabut Odessa R, Ng Hui Xuan, Fernandez Gloria, Yoon Keejung, Kuhn Jeremy, Pleasure Samuel J
Department of Neurology, University of California San Francisco, San Francisco, CA 94158, USA.
College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, Korea.
J Dev Biol. 2016 Dec;4(4). doi: 10.3390/jdb4040029. Epub 2016 Sep 29.
Neural progenitors in the embryonic neocortex must be tightly regulated in order to generate the correct number and projection neuron subtypes necessary for the formation of functional neocortical circuits. In this study, we show that the intracellular protein Suppressor of Fused (Sufu) regulates the proliferation of intermediate progenitor (IP) cells at later stages of corticogenesis to affect the number of Cux1+ upper layer neurons in the postnatal neocortex. This correlates with abnormal levels of the repressor form of Gli3 (Gli3R) and the ectopic expression of Patched 1 (Ptch1), a Sonic Hedgehog (Shh) target gene. These studies reveal that the canonical role of Sufu as an inhibitor of Shh signaling is conserved at later stages of corticogenesis and that Sufu plays a crucial role in regulating neuronal number by controlling the cell cycle dynamics of IP cells in the embryonic neocortex.
胚胎新皮层中的神经祖细胞必须受到严格调控，才能产生形成功能性新皮层回路所需的正确数量和投射神经元亚型。在本研究中，我们表明细胞内蛋白Fused抑制因子（Sufu）在皮质发生的后期调节中间祖细胞（IP）的增殖，从而影响出生后新皮层中Cux1+上层神经元的数量。这与Gli3阻遏形式（Gli3R）的异常水平以及Sonic Hedgehog（Shh）靶基因Patched 1（Ptch1）的异位表达相关。这些研究表明，Sufu作为Shh信号抑制剂的经典作用在皮质发生后期得以保留，并且Sufu在通过控制胚胎新皮层中IP细胞的细胞周期动态来调节神经元数量方面发挥着关键作用。
