Profile

My laboratory addresses two areas of importance to vision. In the first, we study the cellular and molecular mechanisms governing mouse retinal development, from the initial patterning events of the optic neuroepithelium through specification of cell fate in the proliferative and multipotential retinal progenitor cells and their postmitotic progeny. Our work incorporates multiple genetic models that are helping us to identify the genetic circuitry driving these processes. The second topic is to understand how the resident retinal glia (Muller glia) contribute to the pathological changes associated with retinal disease and injury, and to discover ways to stimulate regeneration from these cells. We are particularly interested in understanding how the Muller glia alter their differentiation program in retinal injury and proliferative vitreoretinopathy as these situations best reveal the complexity of the barriers to regeneration. Through the Audacious Goals Initiative from the National Eye Institute, we have begun a screen of small molecules and exosomes from various cell sources to identify novel factors that promote regenerative properties in adult mouse Muller glia in vivo. Our research incorporates mouse genetics, cell and tissue culture, analyses of protein and RNA expression, gene regulation, non-invasive live ocular imaging, fixed sample imaging, and examination of cellular behavior.

Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Differential Expression of NF2 in Neuroepithelial Compartments Is Necessary for Mammalian Eye Development. Moon KH, Kim HT, Lee D, Rao MB, Levine EM, Lim DS, Kim JW (2018) Dev Cell 44(1): 13-28.e3
    › Primary publication · 29249622 (PubMed) · PMC5760287 (PubMed Central)
  2. Müller glial microRNAs are required for the maintenance of glial homeostasis and retinal architecture. Wohl SG, Jorstad NL, Levine EM, Reh TA (2017) Nat Commun 8(1): 1603
    › Primary publication · 29150673 (PubMed) · PMC5693933 (PubMed Central)
  3. Lef1-dependent hypothalamic neurogenesis inhibits anxiety. Xie Y, Kaufmann D, Moulton MJ, Panahi S, Gaynes JA, Watters HN, Zhou D, Xue HH, Fung CM, Levine EM, Letsou A, Brennan KC, Dorsky RI (2017) PLoS Biol 15(8): e2002257
    › Primary publication · 28837622 (PubMed) · PMC5570277 (PubMed Central)
  4. The LIM protein complex establishes a retinal circuitry of visual adaptation by regulating Pax6 α-enhancer activity. Kim Y, Lim S, Ha T, Song YH, Sohn YI, Park DJ, Paik SS, Kim-Kaneyama JR, Song MR, Leung A, Levine EM, Kim IB, Goo YS, Lee SH, Kang KH, Kim JW (2017) Elife
    › Primary publication · 28139974 (PubMed) · PMC5308899 (PubMed Central)
  5. The RNA Binding Protein Igf2bp1 Is Required for Zebrafish RGC Axon Outgrowth In Vivo. Gaynes JA, Otsuna H, Campbell DS, Manfredi JP, Levine EM, Chien CB (2015) PLoS One 10(9): e0134751
    › Primary publication · 26325373 (PubMed) · PMC4556669 (PubMed Central)
  6. Genetic chimeras reveal the autonomy requirements for Vsx2 in embryonic retinal progenitor cells. Sigulinsky CL, German ML, Leung AM, Clark AM, Yun S, Levine EM (2015) Neural Dev : 12
    › Primary publication · 25927996 (PubMed) · PMC4450477 (PubMed Central)
  7. Retinal pigment epithelium development, plasticity, and tissue homeostasis. Fuhrmann S, Zou C, Levine EM (2014) Exp Eye Res : 141-50
    › Primary publication · 24060344 (PubMed) · PMC4087157 (PubMed Central)
  8. Lhx2 balances progenitor maintenance with neurogenic output and promotes competence state progression in the developing retina. Gordon PJ, Yun S, Clark AM, Monuki ES, Murtaugh LC, Levine EM (2013) J Neurosci 33(30): 12197-207
    › Primary publication · 23884928 (PubMed) · PMC3721834 (PubMed Central)
  9. ASCL1 reprograms mouse Muller glia into neurogenic retinal progenitors. Pollak J, Wilken MS, Ueki Y, Cox KE, Sullivan JM, Taylor RJ, Levine EM, Reh TA (2013) Development 140(12): 2619-31
    › Primary publication · 23637330 (PubMed) · PMC3666387 (PubMed Central)
  10. CDC42 is required for tissue lamination and cell survival in the mouse retina. Heynen SR, Meneau I, Caprara C, Samardzija M, Imsand C, Levine EM, Grimm C (2013) PLoS One 8(1): e53806
    › Primary publication · 23372671 (PubMed) · PMC3553133 (PubMed Central)
  11. Vsx2 controls eye organogenesis and retinal progenitor identity via homeodomain and non-homeodomain residues required for high affinity DNA binding. Zou C, Levine EM (2012) PLoS Genet 8(9): e1002924
    › Primary publication · 23028343 (PubMed) · PMC3447932 (PubMed Central)
  12. Cyclin D1 inactivation extends proliferation and alters histogenesis in the postnatal mouse retina. Das G, Clark AM, Levine EM (2012) Dev Dyn 241(5): 941-52
    › Primary publication · 22434780 (PubMed) · PMC3361900 (PubMed Central)
  13. Proliferative reactive gliosis is compatible with glial metabolic support and neuronal function. Vázquez-Chona FR, Swan A, Ferrell WD, Jiang L, Baehr W, Chien WM, Fero M, Marc RE, Levine EM (2011) BMC Neurosci : 98
    › Primary publication · 21985191 (PubMed) · PMC3203081 (PubMed Central)
  14. Lhx2 links the intrinsic and extrinsic factors that control optic cup formation. Yun S, Saijoh Y, Hirokawa KE, Kopinke D, Murtaugh LC, Monuki ES, Levine EM (2009) Development 136(23): 3895-906
    › Primary publication · 19906857 (PubMed) · PMC2778739 (PubMed Central)
  15. Cyclin D1 fine-tunes the neurogenic output of embryonic retinal progenitor cells. Das G, Choi Y, Sicinski P, Levine EM (2009) Neural Dev : 15
    › Primary publication · 19416500 (PubMed) · PMC2694796 (PubMed Central)
  16. Rlbp1 promoter drives robust Müller glial GFP expression in transgenic mice. Vázquez-Chona FR, Clark AM, Levine EM (2009) Invest Ophthalmol Vis Sci 50(8): 3996-4003
    › Primary publication · 19324864 (PubMed)
  17. Vsx2/Chx10 ensures the correct timing and magnitude of Hedgehog signaling in the mouse retina. Sigulinsky CL, Green ES, Clark AM, Levine EM (2008) Dev Biol 317(2): 560-75
    › Primary publication · 18417110 (PubMed) · PMC2671289 (PubMed Central)
  18. Expression patterns and cell cycle profiles of PCNA, MCM6, cyclin D1, cyclin A2, cyclin B1, and phosphorylated histone H3 in the developing mouse retina. Barton KM, Levine EM (2008) Dev Dyn 237(3): 672-82
    › Primary publication · 18265020 (PubMed)
  19. Negative regulation of Vsx1 by its paralog Chx10/Vsx2 is conserved in the vertebrate retina. Clark AM, Yun S, Veien ES, Wu YY, Chow RL, Dorsky RI, Levine EM (2008) Brain Res : 99-113
    › Primary publication · 17919464 (PubMed) · PMC3315787 (PubMed Central)
  20. Defects in retinal pigment epithelium cell proliferation and retinal attachment in mutant mice with p27(Kip1) gene ablation. Defoe DM, Adams LB, Sun J, Wisecarver SN, Levine EM (2007) Mol Vis : 273-86
    › Primary publication · 17356514 (PubMed) · PMC2633469 (PubMed Central)
  21. Absence of chx10 causes neural progenitors to persist in the adult retina. Dhomen NS, Balaggan KS, Pearson RA, Bainbridge JW, Levine EM, Ali RR, Sowden JC (2006) Invest Ophthalmol Vis Sci 47(1): 386-96
    › Primary publication · 16384989 (PubMed) · PMC2423807 (PubMed Central)
  22. Cell cycling through development. Levine EM (2004) Development 131(10): 2241-6
    › Primary publication · 15128665 (PubMed)
  23. Cell-intrinsic regulators of proliferation in vertebrate retinal progenitors. Levine EM, Green ES (2004) Semin Cell Dev Biol 15(1): 63-74
    › Primary publication · 15036209 (PubMed)
  24. Expression of the cyclin-dependent kinase inhibitor p27Kip1 by developing retinal pigment epithelium. Defoe DM, Levine EM (2003) Gene Expr Patterns 3(5): 615-9
    › Primary publication · 12971995 (PubMed)
  25. Retinal remodeling triggered by photoreceptor degenerations. Jones BW, Watt CB, Frederick JM, Baehr W, Chen CK, Levine EM, Milam AH, Lavail MM, Marc RE (2003) J Comp Neurol 464(1): 1-16
    › Primary publication · 12866125 (PubMed)
  26. Hes1 but not Hes5 regulates an astrocyte versus oligodendrocyte fate choice in glial restricted precursors. Wu Y, Liu Y, Levine EM, Rao MS (2003) Dev Dyn 226(4): 675-89
    › Primary publication · 12666205 (PubMed)
  27. Genetic rescue of cell number in a mouse model of microphthalmia: interactions between Chx10 and G1-phase cell cycle regulators. Green ES, Stubbs JL, Levine EM (2003) Development 130(3): 539-52
    › Primary publication · 12490560 (PubMed)
  28. The cyclin-dependent kinase inhibitors p19(Ink4d) and p27(Kip1) are coexpressed in select retinal cells and act cooperatively to control cell cycle exit. Cunningham JJ, Levine EM, Zindy F, Goloubeva O, Roussel MF, Smeyne RJ (2002) Mol Cell Neurosci 19(3): 359-74
    › Primary publication · 11906209 (PubMed)
  29. Extraocular mesenchyme patterns the optic vesicle during early eye development in the embryonic chick. Fuhrmann S, Levine EM, Reh TA (2000) Development 127(21): 4599-609
    › Primary publication · 11023863 (PubMed)
  30. Soluble factors and the development of rod photoreceptors. Levine EM, Fuhrmann S, Reh TA (2000) Cell Mol Life Sci 57(2): 224-34
    › Primary publication · 10766019 (PubMed)
  31. p27(Kip1) regulates cell cycle withdrawal of late multipotent progenitor cells in the mammalian retina. Levine EM, Close J, Fero M, Ostrovsky A, Reh TA (2000) Dev Biol 219(2): 299-314
    › Primary publication · 10694424 (PubMed)
  32. The nuclear receptor transcription factor, retinoid-related orphan receptor beta, regulates retinal progenitor proliferation. Chow L, Levine EM, Reh TA (1998) Mech Dev 77(2): 149-64
    › Primary publication · 9831642 (PubMed)
  33. Multipotential stem cells and progenitors in the vertebrate retina. Reh TA, Levine EM (1998) J Neurobiol 36(2): 206-20
    › Primary publication · 9712305 (PubMed)
  34. Vsx-1 and Vsx-2: differential expression of two paired-like homeobox genes during zebrafish and goldfish retinogenesis. Passini MA, Levine EM, Canger AK, Raymond PA, Schechter N (1997) J Comp Neurol 388(3): 495-505
    › Primary publication · 9368856 (PubMed)
  35. Vsx-1 and Vsx-2: two Chx10-like homeobox genes expressed in overlapping domains in the adult goldfish retina. Levine EM, Passini M, Hitchcock PF, Glasgow E, Schechter N (1997) J Comp Neurol 387(3): 439-48
    › Primary publication · 9335426 (PubMed)
  36. Sonic hedgehog promotes rod photoreceptor differentiation in mammalian retinal cells in vitro. Levine EM, Roelink H, Turner J, Reh TA (1997) J Neurosci 17(16): 6277-88
    › Primary publication · 9236238 (PubMed)
  37. Homeobox genes are expressed in the retina and brain of adult goldfish. Levine EM, Schechter N (1993) Proc Natl Acad Sci U S A 90(7): 2729-33
    › Primary publication · 8096640 (PubMed) · PMC46169 (PubMed Central)
  38. Cloning of multiple forms of goldfish vimentin: differential expression in CNS. Glasgow E, Druger RK, Fuchs C, Levine EM, Giordano S, Schechter N (1994) J Neurochem 63(2): 470-81
    › Primary publication · 8035174 (PubMed)
  39. Restricted expression of a new paired-class homeobox gene in normal and regenerating adult goldfish retina. Levine EM, Hitchcock PF, Glasgow E, Schechter N (1994) J Comp Neurol 348(4): 596-606
    › Primary publication · 7836564 (PubMed)
  40. Complex expression of keratins in goldfish optic nerve. Druger RK, Glasgow E, Fuchs C, Levine EM, Matthews JP, Park CY, Schechter N (1994) J Comp Neurol 340(2): 269-80
    › Primary publication · 7515399 (PubMed)
  41. Plasticin, a novel type III neurofilament protein from goldfish retina: increased expression during optic nerve regeneration. Glasgow E, Druger RK, Levine EM, Fuchs C, Schechter N (1992) Neuron 9(2): 373-81
    › Primary publication · 1379821 (PubMed)
  42. Cloning of a type I keratin from goldfish optic nerve: differential expression of keratins during regeneration. Druger RK, Levine EM, Glasgow E, Jones PS, Schechter N (1992) Differentiation 52(1): 33-43
    › Primary publication · 1283739 (PubMed)