Hsf4在视网膜发育中的作用及机制

The vertebrate retina comprises six classes of neurons and one class of glial cells, all derived from a population of multipotent progeitors. Retinogenesis in mice is completed at approximately postnatal day 10. Abnormal postnatal retina development was found in Hsf4 KO mice. Moreover, the changes of retina development were showed to be in the same position with the Hsf4 expression. All these data indicated that the loss of Hsf4 may involve in this abnormal development process. In this proposal, we planed to start our study on the abnormal retinal development in Hsf4 KO mice. With HSF4-ChIP-seq, microdissection and realtime PCR, the exactly abnormal group of cells and transcriptional factors involved in Hsf4 related differentiation process are going to be identified. Moreover, lenti-virus transfection of specific factor with wholemount cultured Hsf4 KO mice to identify whether or not it will compensate the loss function of HSF4. Fulfilling this proposal will provide a mechanism that elucidate the role of HSF4 in retina differentiation, which may contribute to the retina regenerative medicine.

Hsf4是近年发现的参与眼睛发育的重要转录因子。Hsf4基因敲除小鼠表现出多种眼发育的异常，主要表现为小眼症，晶状体分化不良，视网膜发育紊乱。我们在前期研究中发现，在Hsf4基因敲除小鼠视网膜中发生形态紊乱的部位与正常小鼠Hsf4表达的部位一致。这说明，Hsf4的基因敲除影响了视网膜的分化和发育。本项目拟在已有工作的基础上，对HSF4在小鼠视网膜发育中的作用进行研究。通过ChIP-seq,realtime PCR，激光显微切割等技术手段结合视网膜体外分化体系，研究HSF4缺失影响的细胞群和转录调控靶点；同时在Hsf4基因敲除小鼠中通过慢病毒技术进行敲除或过表达关键靶点因子，研究其能够逆转Hsf4基因敲除小鼠的视网膜异常，揭示Hsf4在视网膜发育中的作用。本课题的完成将揭示Hsf4在视网膜正常发育中的新机制，完善视网膜发育分化的理论基础，并有益于视网膜再生医学发展。