Differential Expression of NF2 in Neuroepithelial Compartments Is Necessary for Mammalian Eye Development

Publication date: Available online 14 December 2017
Source:Developmental Cell
Author(s): Kyeong Hwan Moon, Hyoung-Tai Kim, Dahye Lee, Mahesh B. Rao, Edward M. Levine, Dae-Sik Lim, Jin Woo Kim
The optic neuroepithelial continuum of vertebrate eye develops into three differentially growing compartments: the retina, the ciliary margin (CM), and the retinal pigment epithelium (RPE). Neurofibromin 2 (Nf2) is strongly expressed in slowly expanding RPE and CM compartments, and the loss of mouse Nf2 causes hyperplasia in these compartments, replicating the ocular abnormalities seen in human NF2 patients. The hyperplastic ocular phenotypes were largely suppressed by heterozygous deletion of Yap and Taz, key targets of the Nf2-Hippo signaling pathway. We also found that, in addition to feedback transcriptional regulation of Nf2 by Yap/Taz in the CM, activation of Nf2 expression by Mitf in the RPE and suppression by Sox2 in retinal progenitor cells are necessary for the differential growth of the corresponding cell populations. Together, our findings reveal that Nf2 is a key player that orchestrates the differential growth of optic neuroepithelial compartments during vertebrate eye development.

Graphical abstract

Teaser

Moon et al. identify a mechanism underlying the differential growth of optic neuroepithelial compartments in the mouse eye. Differential transcriptional regulation of the tumor suppressor neurofibromin 2 (Nf2) in each neuroepithelial compartment is necessary for the differential growth of the tissue.


http://ift.tt/2j6iUp2