The Spatiotemporal Expression Profile And Function Of LncRNA T-uc.189 During Early Mouse Cerebral Cortex Development

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.