Approximately 10% of humans with anophthalmia (absent eye) or severe microphthalmia (small eye) show haploid insufficiency due to mutations in SOX2, ...
SOX2 is a dose-dependent regulator of retinal neural progenitor competence Olena V. Taranova,1,3 Scott T. Magness,1,3 B. Matthew Fagan,1 Yongqin Wu,2 Natalie Surzenko,1 Scott R. Hutton,1 and Larysa H. Pevny1,4 1
Department of Genetics and 2Neuroscience Center In Situ Hybridization Core Facility, University of North Carolina Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Approximately 10% of humans with anophthalmia (absent eye) or severe microphthalmia (small eye) show haploid insufficiency due to mutations in SOX2, a SOXB1-HMG box transcription factor. However, at present, the molecular or cellular mechanisms responsible for these conditions are poorly understood. Here, we directly assessed the requirement for SOX2 during eye development by generating a gene-dosage allelic series of Sox2 mutations in the mouse. The Sox2 mutant mice display a range of eye phenotypes consistent with human syndromes and the severity of these phenotypes directly relates to the levels of SOX2 expression found in progenitor cells of the neural retina. Retinal progenitor cells with conditionally ablated Sox2 lose competence to both proliferate and terminally differentiate. In contrast, in Sox2 hypomorphic/null mice, a reduction of SOX2 expression to
