Abstract

Specification of neural progenitors in the central nervous system (CNS) and maintenance of their proliferative and differentiation capacities largely depend on the function of transcription factors. One such transcription factor, expressed in all neural progenitors of the CNS, is SOX2. We have shown that SOX2 is required for proliferation and differentiation of retinal neural progenitors. Furthermore, we have shown that lowering expression levels of SOX2 (below 40%) in mice results in restriction in retinal progenitor competence and leads to anophthalmia and microphthalmia--conditions observed in 10% of humans with haploid insufficiency in SOX2. Based on these findings we hypothesize that SOX2 functions to specify retinal neural progenitors and to maintain their proliferative and differentiation capacity during the course of retinogenesis. In this study, we will directly assess the effects of Sox2 ablation and reducing its expression levels on the properties of temporally distinct populations of retinal progenitors. PUBLIC HEALTH REVELANCE: We will utilize mouse genetic tools and cellular assays to dissect the molecular mechanisms affected by the expression levels of SOX2 in retinal progenitors.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY018261-08
Application #
7797381
Study Section
Neurogenesis and Cell Fate Study Section (NCF)
Program Officer
Greenwell, Thomas
Project Start
2008-04-01
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
8
Fiscal Year
2010
Total Cost
$418,800
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Genetics
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Heavner, Whitney E; Andoniadou, Cynthia L; Pevny, Larysa H (2014) Establishment of the neurogenic boundary of the mouse retina requires cooperation of SOX2 and WNT signaling. Neural Dev 9:27
Langer, Lee; Sulik, Kathleen; Pevny, Larysa (2014) Cleft Palate in a Mouse Model of SOX2 Haploinsufficiency. Cleft Palate Craniofac J 51:110-4
Surzenko, Natalia; Crowl, Tessa; Bachleda, Amelia et al. (2013) SOX2 maintains the quiescent progenitor cell state of postnatal retinal Muller glia. Development 140:1445-56
Langer, Lee; Taranova, Olena; Sulik, Kathleen et al. (2012) SOX2 hypomorphism disrupts development of the prechordal floor and optic cup. Mech Dev 129:1-12
Matsushima, Danielle; Heavner, Whitney; Pevny, Larysa H (2011) Combinatorial regulation of optic cup progenitor cell fate by SOX2 and PAX6. Development 138:443-54
Pevny, Larysa H; Nicolis, Silvia K (2010) Sox2 roles in neural stem cells. Int J Biochem Cell Biol 42:421-4