神经发生是一个复杂的过程，依赖于空间和时间上对基因表达的精细调控。神

经元迁移和神经祖细胞(neural progenitor cells, NPCs)的增殖分化是大脑正常形成

和功能发挥的基础生物学过程，神经元的异常迁移和 NPCs 的增殖分化紊乱将导

致了一系列神经疾病和脑损伤。然而，调控这一过程的分子机制仍然是未知的。

本实验室前期工作发现 481 个 T-UCRs（Transcribed ultra-conserved region）中

的 50 个可以在小鼠、恒河猴及人三个物种的神经系统中表达，其中 T-uc.189 在

小鼠早期神经系统发育过程中表达量较高且随着发育的进行表达量逐渐降低，并

且该 lncRNA 的宿主基因 Srsf3 是影响神经发育的重要剪接因子。

在本研究中，我们首先通过 RACE 实验获取了 T-uc.189 转录本全长序列。并

且通过原位杂交实验检测了 T-uc.189 在小鼠早期胚胎脑发育过程中的时空表达

谱，我们发现 T-uc.189 主要集中表达在脑室区(Ventricular zone, VZ)，并随着大脑

成熟表达量逐渐减少。为进一步对 T-uc.189 的生物学功能进行探究，我们通过鼠

胚电击实验对其进行在体敲低，我们发现敲低 T-uc.189 可明显抑制神经元的迁移，

促进 NPCs 增殖，抑制 NPCs 向神经元的分化。有文献报道 T-UCRs 多数可通过

调控与其基因组座位相同的蛋白编码基因的表达而发挥生物学功能，随后我们检

测 T-uc.189 对其宿主基因 Srsf3（serine-arginine-rich splicing factor 3）是否有调控

作用，我们分别通过 Real-time PCR 及 Western blot 实验检测 T-uc.189 敲低/过表

达后 Srsf3 在 mRNA 水平及蛋白水平的表达量变化情况，我们发现 T-uc.189 对

Srsf3 的表达有正向调控作用。随后在体生物学功能实验证明 Srsf3 敲低后呈现与

T-uc.189 敲低相似的生物学功能异常，并且过表达 Srsf3 后可回复正常生物学功

能。综上，我们研究发现 T-uc.189 可通过正向调控 Srsf3 的表达进而影响小鼠大

脑皮层发育过程。

Neurogenesis is a complex process that depends on the fine regulation of gene

expression in spatial and temporal control. The migration of neurons and the

proliferation and differentiation of neural progenitor cells (NPCs) are the basic

biological processes for the normal formation and function of the brain. The abnormal

migration of neurons and the disorder of the proliferation and differentiation of NPCs

will lead to a series of neurological diseases and brain injuries. However, the molecular

mechanisms that regulate this process are still unknown. Preliminary work in our lab,

50 of the 481 T-UCRs were found in three species of mice, rhesus monkeys and human

expressed in the nervous system, including T - uc.189. In the process of development

of the nervous system in early embryonic brain, T-uc.189 shows in higher quantity and

presents a dynamic change, and the host gene of T-uc.189, Srsf3, is one of the

important splicing factor that affect the neural development.

In this study, we first obtained the full-length sequence of T-uc.189 transcript

through RACE experiment. In addition, the temporal and spatial expression profile of

T-uc.189 during the early embryonic brain development of mice was detected by in

situ hybridization. It was found that the expression of T-uc.189 was mainly

concentrated in the ventricle region (VZ), and gradually decreased with brain

maturation. In order to further explore the biological function of T-uc.189, we detected

it in vivo through the in utero electroporation, and we found that knockdown T-uc.189

can significantly inhibit the migration of neurons, promote the proliferation of NPCs,

and inhibit the differentiation of NPCs into neurons. Have reported T-UCRs most

could regulate and control their host gene expression and affect biological functions,

then we detect the host gene of T-uc.189, serine-arginine-rich splicing factor 3 (Srsf3)

whether there is a regulation function, we respectively detect Srsf3 expression level by

Real - time PCR and Western blot experiments after T-uc.189 expression level

changed, we found that T-uc.189 had a positive regulation effect on the expression of

Srsf3. And then in vivo biological function experiments showed that Srsf3 knockdown

presented biological function abnormalities similar to T-uc.189 knockdown, and the

overexpression of Srsf3 could restore normal biological function that T-uc.189

knockdown caused. In conclusion, our study found that T-uc.189 can affect the

embryonic brain development process of mice by regulating the expression of its host

gene Srsf3.