Open AccessRegulation of WNT Signaling by VSX2 During Optic Vesicle Patterning in Human Induced Pluripotent Stem Cells
Author(s) -
Capowski Elizabeth E.,
Wright Lynda S.,
Liang Kun,
Phillips M. Joseph,
Wallace Kyle,
Petelinsek Anna,
Hagstrom Anna,
Pinilla Isabel,
Borys Katarzyna,
Lien Jessica,
Min Jee Hong,
Keles Sunduz,
Thomson James A.,
Gamm David M.
Publication year - 2016
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2414
Subject(s) - wnt signaling pathway , biology , microbiology and biotechnology , regulator , mutant , stem cell , homeobox , induced pluripotent stem cell , downregulation and upregulation , signal transduction , genetics , gene expression , gene , embryonic stem cell
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. S tem C ells 2016;34:2625–2634