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

Developmental cell | 2018

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.

Pubmed ID: 29249622 RIS Download

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Associated grants

  • Agency: NEI NIH HHS, United States
    Id: R01 EY013760

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Olympus Fluoview FV10-ASW (tool)

RRID:SCR_014215

Image processing software used to modify and clarify sample images for FluoView FV1000 range of confocal laser scanning microscopes and Fluoview FV1000MPE multiphoton excitation systems. The software incorporates high-dynamic-range imaging, minimized signal-to-noise ratios, partial stitching with multiarea time-lapse imaging, and channel unmixing. The software also allows users to select specific areas of the whole sample, which can stitched together.

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β-Catenin Antibody (antibody)

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Anti-phospho-Histone H3 (Ser10) Antibody (antibody)

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This unknown targets phospho-Histone H3 (Ser10)

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YAP/TAZ (D24E4) Rabbit mAb (antibody)

RRID:AB_10950494

This monoclonal targets Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Asp362 of human TAZ protein

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Neuronal Class III beta-Tubulin (TUJ1) Monoclonal Antibody, Purified (antibody)

RRID:AB_2313773

This monoclonal targets Neuronal Class III beta-Tubulin (TUJ1) Purified

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Anti-Sox9 (antibody)

RRID:AB_2239761

This polyclonal targets Sox9

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RRID:AB_2286684

This polyclonal targets SOX2

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Anti-Recoverin (antibody)

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This polyclonal targets Rcvrn

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PKC alpha (C-20) (antibody)

RRID:AB_2168668

This polyclonal targets PRKCA, PRKCG, PRKCB

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Anti-Pals1 (antibody)

RRID:AB_441951

This polyclonal targets Pals1

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Notch2 (D76A6) XP Rabbit mAb (antibody)

RRID:AB_10693319

This recombinant monoclonal targets Notch2

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Human/Mouse MSX1 Affinity Purified Polyclonal Ab (antibody)

RRID:AB_2148804

This polyclonal targets Human/Mouse MSX1 Affinity Purified Ab

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MiTF antibody - ChIP Grade (antibody)

RRID:AB_10902226

This polyclonal targets MiTF antibody - ChIP Grade

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Brn-3b (N-15) (antibody)

RRID:AB_2167529

This polyclonal targets POU4F2

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RRID:AB_10128910

This monoclonal targets Aquaporin-1

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B6.Cg-Mitfmi-sp Mitfmi-vga9/Mmmh (organism)

RRID:MMRRC_009963-MU

Mus musculus with name B6.Cg-Mitfmi-sp Mitfmi-vga9/Mmmh from MMRRC.

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B6.Cg-Tg(Nes-cre)1Kln/J (organism)

RRID:IMSR_JAX:003771

Mus musculus with name B6.Cg-Tg(Nes-cre)1Kln/J from IMSR.

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STOCK Sox2tm1.1Lan/J (organism)

RRID:IMSR_JAX:013093

Mus musculus with name STOCK Sox2tm1.1Lan/J from IMSR.

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FVB.129P2-Nf2tm2Gtn/GvnRbrc (organism)

RRID:IMSR_RBRC02344

Mus musculus with name FVB.129P2-Nf2tm2Gtn/GvnRbrc from IMSR.

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Hep-G2 (cell line)

RRID:CVCL_0027

Cell line Hep-G2 is a Cancer cell line with a species of origin Homo sapiens (Human)

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