Neurofibromatosis 2 (Nf2) is a key determinant for differential growth of optic neuroepithelial compartments

Abstract

Vertebrate eye development accompanies regional diversification of proliferative potential in the optic neuroepithelium, which is partitioned into three compartments？the retina, retinal pigment epithelium (RPE), and ciliary margin zone (CMZ). In this study, I investigated the functions of mouse neurofibromatosis 2 (Nf2), in the development of optic neuroepithelium-derived tissues. I found that the loss of Nf2 in the optic neuroepithelium lead to microphthalmia. Also, structural defects resulted from severe overgrowth of the pigmented cell population in the RPE. I also found that Nf2-deficiency resulted in a hyperplasic CMZ and expansion of CMZ-derived retinal precursor cells. Using a genetic approach, I demonstrated that Nf2, in the RPE and CMZ, is necessary for limiting Yap/Taz activity via the Hippo pathway. Finally, I provide evidences on the transcriptional regulation of Nf2 expression by microphthalmia-inducing transcription factor (Mitf) in the RPE, and by sex-determining region Y-box 2 (Sox2) in the CMZ (and neural retina). Collectively, this study reveals that Nf2 is a key regulator that differentiates the growth of the optic neuroepithelium for achieving proper eye development.