Long non-coding RNAs (lncRNAs) regulate transcription to control development and homeostasis in a variety of tissues and organs. However, their roles in the development of the cerebral cortex have not been well elucidated. Here, a bioinformatics pipeline was applied to delineate the dynamic expression and potential cis-regulating effects of mouse lncRNAs using transcriptome data from 8 embryonic time points and sub-regions of the developing cerebral cortex. We further characterized a sense lncRNA, SenZfp536, which is transcribed downstream of and partially overlaps with the protein-coding gene Zfp536. Both SenZfp536 and Zfp536 were predominantly expressed in the proliferative zone of the developing cortex. Zfp536 was cis-regulated by SenZfp536, which facilitates looping between the promoter of Zfp536 and the genomic region that transcribes SenZfp536. Surprisingly, knocking down or activating the expression of SenZfp536 increased or compromised the proliferation of cortical neural progenitor cells (NPCs), respectively. Finally, overexpressing Zfp536 in cortical NPCs reversed the enhanced proliferation of cortical NPCs caused by SenZfp536 knockdown. The study deepens our understanding of how lncRNAs regulate the propagation of cortical NPCs through cis-regulatory mechanisms.

长链非编码 RNA (lncRNA) 调节转录以控制各种组织和器官的发育和体内平衡。然而，它们在大脑皮层发育中的作用尚未得到很好的阐明。在这里，利用来自 8 个胚胎时间点和发育中大脑皮层子区域的转录组数据，应用生物信息学管道来描绘小鼠 lncRNA 的动态表达和潜在的顺式调节作用。我们进一步表征了有义 lncRNA SenZfp536 ，它在蛋白质编码基因Zfp536的下游转录并部分重叠。SenZfp536和Zfp536都主要在发育皮层的增殖区表达。Zfp536由SenZfp536顺式调节，这促进了 Zfp536 的启动子和转录SenZfp536的基因组区域之间的循环。令人惊讶的是，敲除或激活SenZfp536的表达分别增加或损害了皮质神经祖细胞 (NPC) 的增殖。最后，在皮质 NPC 中过表达Zfp536逆转了由SenZfp536敲低引起的皮质 NPC 增殖增强。该研究加深了我们对 lncRNA 如何通过顺式调节机制调节皮质 NPC 传播的理解。