2. Academic Validation
  3. Regulation of WNT Signaling by VSX2 During Optic Vesicle Patterning in Human Induced Pluripotent Stem Cells

Regulation of WNT Signaling by VSX2 During Optic Vesicle Patterning in Human Induced Pluripotent Stem Cells

  • Stem Cells. 2016 Nov;34(11):2625-2634. doi: 10.1002/stem.2414.
Elizabeth E Capowski 1,  Lynda S Wright 1 2,  Kun Liang 3,  M Joseph Phillips 1 2,  Kyle Wallace 1,  Anna Petelinsek 1,  Anna Hagstrom 1,  Isabel Pinilla 4 5,  Katarzyna Borys 1,  Jessica Lien 1,  Jee Hong Min 1,  Sunduz Keles 6,  James A Thomson 7,  David M Gamm 1 2 8
Affiliations

Affiliations

  • 1 Waisman Center, University of Wisconsin-Madison, Madison, WI, 53705, USA.
  • 2 McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, WI, 53705, USA.
  • 3 Statistics and Actuarial Science, University of Waterloo, Waterloo, ON, Canada.
  • 4 Aragon Institute for Health Research (IIS Aragón), Lozano Blesa University Hospital, Zaragoza, 50009, Spain.
  • 5 Department of Ophthalmology, Lozano Blesa University Hospital, Zaragoza, 50009, Spain.
  • 6 Department of Statistics, University of Wisconsin-Madison, Madison, WI, 53706, USA.
  • 7 Morgridge Institute for Research, Madison, WI, 53715, USA.
  • 8 Department of Ophthamology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, 53705, USA.
PMID: 27301076 DOI: 10.1002/stem.2414
Abstract

Few gene targets of Visual System Homeobox 2 (VSX2) have been identified despite its broad and critical role in the maintenance of neural retina (NR) fate during early retinogenesis. We performed VSX2 ChIP-seq and ChIP-PCR assays on early stage optic vesicle-like structures (OVs) derived from human iPS cells (hiPSCs), which highlighted Wnt pathway genes as direct regulatory targets of VSX2. Examination of early NR patterning in hiPSC-OVs from a patient with a functional null mutation in VSX2 revealed mis-expression and upregulation of Wnt pathway components and retinal pigmented epithelium (RPE) markers in comparison to control hiPSC-OVs. Furthermore, pharmacological inhibition of Wnt signaling rescued the early mutant phenotype, whereas augmentation of Wnt signaling in control hiPSC-OVs phenocopied the mutant. These findings reveal an important role for VSX2 as a regulator of Wnt signaling and suggest that VSX2 may act to maintain NR identity at the expense of RPE in part by direct repression of Wnt pathway constituents. Stem Cells 2016;34:2625-2634.

Keywords

Human induced pluripotent stem cells (hiPSCs); VSX2; WNT; optic vesicles.

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