Faculty Appointments
Associate Professor of Ophthalmology & Visual Sciences
Associate Professor of Cell & Developmental Biology
Education
Ph.D., Biology, Albert Ludwigs University of Freiburg, Freiburg, GermanyM.S., Biology, University of Oldenburg, Oldenburg, Not Specified, Germany
Office Address
Dept. of Ophthalmology and Visual Sciences
Vanderbilt Eye Institute
Vanderbilt University Medical Center
11425 Langford MRB IV
2213 Garland Ave.
Nashville, TN 37232
Vanderbilt Eye Institute
Vanderbilt University Medical Center
11425 Langford MRB IV
2213 Garland Ave.
Nashville, TN 37232
Research Description
Cellular and molecular mechanisms regulating vertebrate eye patterning/differentiation and regeneration.
Organogenesis of the eye is a multi-step process that starts with the formation of optic vesicles followed by invagination of the distal domain and the overlying lens placode, resulting in morphogenesis of the optic cup. The late optic vesicle becomes patterned into distinct ocular tissues; the neural retina, retinal pigment epithelium (RPE) and optic stalk. Multiple congenital eye disorders, including anophthalmia or microphthalmia, aniridia, coloboma and retinal dysplasia, stem from dis¬ruptions in embryonic eye development. Thus, it is important to understand the mechanisms that lead to initial specification and differentiation of ocular tissues.
A complex interplay between inductive signals provided by tissue-tissue interactions and cell-intrinsic factors is critical to ensure proper specification of ocular tissues as well as maintenance of RPE cell fate. While several of the extrinsic and intrinsic determinants have been identified, we are just at the beginning to understand how these signals are integrated. In addition, we know very little about the actual output of these interactions.
The goal of our research is to understand the cellular and molecular mechanisms regulating differentiation, morphogenesis and homeostasis of ocular tissues. Questions addressed in our lab include: How is eye development initiated in the anterior neuroepithelium and what factors determine the early steps of eye formation? How is differentiation of ocular tissues controlled? What are the signals involved in these processes and what are their downstream targets? Is there crosstalk between different pathways? How is homeostasis of ocular tissues maintained?
We use conditional inactivation in mice, in combination with tissue culture and biochemical and cell biological approaches to test the function of extracellular signaling pathways (e.g. Wnt signaling) in ocular morphogenesis, RPE induction and differentiation as well as in RPE homeostasis in the adult eye.
Organogenesis of the eye is a multi-step process that starts with the formation of optic vesicles followed by invagination of the distal domain and the overlying lens placode, resulting in morphogenesis of the optic cup. The late optic vesicle becomes patterned into distinct ocular tissues; the neural retina, retinal pigment epithelium (RPE) and optic stalk. Multiple congenital eye disorders, including anophthalmia or microphthalmia, aniridia, coloboma and retinal dysplasia, stem from dis¬ruptions in embryonic eye development. Thus, it is important to understand the mechanisms that lead to initial specification and differentiation of ocular tissues.
A complex interplay between inductive signals provided by tissue-tissue interactions and cell-intrinsic factors is critical to ensure proper specification of ocular tissues as well as maintenance of RPE cell fate. While several of the extrinsic and intrinsic determinants have been identified, we are just at the beginning to understand how these signals are integrated. In addition, we know very little about the actual output of these interactions.
The goal of our research is to understand the cellular and molecular mechanisms regulating differentiation, morphogenesis and homeostasis of ocular tissues. Questions addressed in our lab include: How is eye development initiated in the anterior neuroepithelium and what factors determine the early steps of eye formation? How is differentiation of ocular tissues controlled? What are the signals involved in these processes and what are their downstream targets? Is there crosstalk between different pathways? How is homeostasis of ocular tissues maintained?
We use conditional inactivation in mice, in combination with tissue culture and biochemical and cell biological approaches to test the function of extracellular signaling pathways (e.g. Wnt signaling) in ocular morphogenesis, RPE induction and differentiation as well as in RPE homeostasis in the adult eye.
Research Keywords
Ocular development and regeneration in mouse
Publications
Pathak A, Stanley EM, Hickman FE, Wallace N, Brewer B, Li D, Gluska S, Perlson E, Fuhrmann S, Akassoglou K, Bronfman F, Casaccia P, Burnette DT, Carter BD. Retrograde Degenerative Signaling Mediated by the p75 Neurotrophin Receptor Requires p150Glued Deacetylation by Axonal HDAC1. Dev. Cell. 2018 Aug 8/6/2018; 46(3): 376-387.e7. PMID: 30086304, PMCID: PMC6093198, PII: S1534-5807(18)30554-9, DOI: 10.1016/j.devcel.2018.07.001, ISSN: 1878-1551.
Yang YP, Ma H, Starchenko A, Huh WJ, Li W, Hickman FE, Zhang Q, Franklin JL, Mortlock DP, Fuhrmann S, Carter BD, Ihrie RA, Coffey RJ. A Chimeric Egfr Protein Reporter Mouse Reveals Egfr Localization and Trafficking In Vivo. Cell Rep. 2017 May 5/9/2017; 19(6): 1257-67. PMID: 28494873, PII: S2211-1247(17)30542-9, DOI: 10.1016/j.celrep.2017.04.048, ISSN: 2211-1247.
Alldredge A, Fuhrmann S. Loss of Axin2 Causes Ocular Defects During Mouse Eye Development. Invest. Ophthalmol. Vis. Sci. 2016 Oct 10/1/2016; 57(13): 5253-62. PMID: 27701636, PII: 2565724, DOI: 10.1167/iovs.15-18599, ISSN: 1552-5783.
Bankhead EJ, Colasanto MP, Dyorich KM, Jamrich M, Murtaugh LC, Fuhrmann S. Multiple requirements of the focal dermal hypoplasia gene porcupine during ocular morphogenesis. Am. J. Pathol [print-electronic]. 2015 Jan; 185(1): 197-213. PMID: 25451153, PMCID: PMC4278246, PII: S0002-9440(14)00540-9, DOI: 10.1016/j.ajpath.2014.09.002, ISSN: 1525-2191.
Fuhrmann S, Zou C, Levine EM. Retinal pigment epithelium development, plasticity, and tissue homeostasis. Exp. Eye Res [print-electronic]. 2014 Jun; 123: 141-50. PMID: 24060344, PMCID: PMC4087157, PII: S0014-4835(13)00269-8, DOI: 10.1016/j.exer.2013.09.003, ISSN: 1096-0007.
Kruse-Bend R, Rosenthal J, Quist TS, Veien ES, Fuhrmann S, Dorsky RI, Chien CB. Extraocular ectoderm triggers dorsal retinal fate during optic vesicle evagination in zebrafish. Dev. Biol [print-electronic]. 2012 Nov 11/1/2012; 371(1): 57-65. PMID: 22921921, PMCID: PMC3455121, PII: S0012-1606(12)00435-6, DOI: 10.1016/j.ydbio.2012.08.004, ISSN: 1095-564X.
Westenskow PD, McKean JB, Kubo F, Nakagawa S, Fuhrmann S. Ectopic Mitf in the embryonic chick retina by co-transfection of ß-catenin and Otx2. Invest. Ophthalmol. Vis. Sci [print-electronic]. 2010 Oct; 51(10): 5328-35. PMID: 20463321, PMCID: PMC3066625, PII: iovs.09-5015, DOI: 10.1167/iovs.09-5015, ISSN: 1552-5783.
Bassett EA, Williams T, Zacharias AL, Gage PJ, Fuhrmann S, West-Mays JA. AP-2alpha knockout mice exhibit optic cup patterning defects and failure of optic stalk morphogenesis. Hum. Mol. Genet [print-electronic]. 2010 May 5/1/2010; 19(9): 1791-804. PMID: 20150232, PMCID: PMC2850623, PII: ddq060, DOI: 10.1093/hmg/ddq060, ISSN: 1460-2083.
Fuhrmann S. Eye morphogenesis and patterning of the optic vesicle. Curr. Top. Dev. Biol. 2010; 93: 61-84. PMID: 20959163, PMCID: PMC2958684, PII: B978-0-12-385044-7.00003-5, DOI: 10.1016/B978-0-12-385044-7.00003-5, ISSN: 1557-8933.
Westenskow P, Piccolo S, Fuhrmann S. Beta-catenin controls differentiation of the retinal pigment epithelium in the mouse optic cup by regulating Mitf and Otx2 expression. Development [print-electronic]. 2009 Aug; 136(15): 2505-10. PMID: 19553286, PMCID: PMC2709060, PII: dev.032136, DOI: 10.1242/dev.032136, ISSN: 0950-1991.
Fuhrmann S, Riesenberg AN, Mathiesen AM, Brown EC, Vetter ML, Brown NL. Characterization of a transient TCF/LEF-responsive progenitor population in the embryonic mouse retina. Invest. Ophthalmol. Vis. Sci [print-electronic]. 2009 Jan; 50(1): 432-40. PMID: 18599572, PMCID: PMC2615067, PII: iovs.08-2270, DOI: 10.1167/iovs.08-2270, ISSN: 1552-5783.
Zhang J, Fuhrmann S, Vetter ML. A nonautonomous role for retinal frizzled-5 in regulating hyaloid vitreous vasculature development. Invest. Ophthalmol. Vis. Sci [print-electronic]. 2008 Dec; 49(12): 5561-7. PMID: 18791178, PMCID: PMC2679971, PII: iovs.08-2226, DOI: 10.1167/iovs.08-2226, ISSN: 1552-5783.
Burns CJ, Zhang J, Brown EC, Van Bibber AM, Van Es J, Clevers H, Ishikawa TO, Taketo MM, Vetter ML, Fuhrmann S. Investigation of Frizzled-5 during embryonic neural development in mouse. Dev. Dyn. 2008 Jun; 237(6): 1614-26. PMID: 18489003, PMCID: PMC2562763, DOI: 10.1002/dvdy.21565, ISSN: 1058-8388.
Fuhrmann S. Wnt signaling in eye organogenesis. Organogenesis. 2008 Apr; 4(2): 60-7. PMID: 19122781, PMCID: PMC2613311, ISSN: 1547-6278.
Levine Edward M, Fuhrmann Sabine. An update on the regulation of rod photoreceptor development. In: Ophthal Res Series. Visual Transduction and Non-visual light perception. 4. [place unknown: publisher unknown]; 2008. Review; p. 3-64.
Seydewitz V, Rothermel A, Fuhrmann S, Schneider A, DeGrip WJ, Layer PG, Hofmann HD. Expression of CNTF receptor-alpha in chick violet-sensitive cones with unique morphologic properties. Invest. Ophthalmol. Vis. Sci. 2004 Feb; 45(2): 655-61. PMID: 14744911, ISSN: 0146-0404.
Fuhrmann S, Stark MR, Heller S. Expression of Frizzled genes in the developing chick eye. Gene Expr. Patterns. 2003 Oct; 3(5): 659-62. PMID: 12972002, PII: S1567133X03001078, ISSN: 1567-133X.
Fuhrmann S, Grabosch K, Kirsch M, Hofmann HD. Distribution of CNTF receptor alpha protein in the central nervous system of the chick embryo. J. Comp. Neurol. 2003 Jun 6/16/2003; 461(1): 111-22. PMID: 12722108, DOI: 10.1002/cne.10701, ISSN: 0021-9967.
Fuhrmann S, Levine EM, Reh TA. Extraocular mesenchyme patterns the optic vesicle during early eye development in the embryonic chick. Development. 2000 Nov; 127(21): 4599-609. PMID: 11023863, ISSN: 0950-1991.
Levine EM, Fuhrmann S, Reh TA. Soluble factors and the development of rod photoreceptors. Cell. Mol. Life Sci. 2000 Feb; 57(2): 224-34. PMID: 10766019, PII: 10.1007/PL00000686, DOI: 10.1007/PL00000686, ISSN: 1420-682X.
Fuhrmann S, Chow L, Reh TA. Molecular control of cell diversification in the vertebrate retina. Results Probl Cell Differ. 2000; 31: 69-91. PMID: 10929402, ISSN: 0080-1844.
Fuhrmann S, Heller S, Rohrer H, Hofmann HD. A transient role for ciliary neurotrophic factor in chick photoreceptor development. J. Neurobiol. 1998 Dec; 37(4): 672-83. PMID: 9858267, PII: 10.1002/(SICI)1097-4695(199812)37:4<672::AID-NEU14>3.0.CO;2-1, ISSN: 0022-3034.
Fuhrmann S, Kirsch M, Heller S, Rohrer H, Hofmann HD. Differential regulation of ciliary neurotrophic factor receptor-alpha expression in all major neuronal cell classes during development of the chick retina. J. Comp. Neurol. 1998 Oct 10/19/1998; 400(2): 244-54. PMID: 9766402, PII: 10.1002/(SICI)1096-9861(19981019)400:2<244::AID-CNE6>3.0.CO;2-9, ISSN: 0021-9967.
Kirsch M, Schulz-Key S, Wiese A, Fuhrmann S, Hofmann H. Ciliary neurotrophic factor blocks rod photoreceptor differentiation from postmitotic precursor cells in vitro. Cell Tissue Res. 1998 Feb; 291(2): 207-16. PMID: 9426308, ISSN: 0302-766X.
Fuhrmann S, Kirsch M, Wewetzer K, Hofmann HD. Use of cell ELISA for the screening of neurotrophic activities on minor cell populations in retinal monolayer cultures. J. Neurosci. Methods. 1997 Aug 8/22/1997; 75(2): 199-205. PMID: 9288653, PII: S0165-0270(97)00073-3, ISSN: 0165-0270.
Kirsch M, Fuhrmann S, Wiese A, Hofmann HD. CNTF exerts opposite effects on in vitro development of rat and chick photoreceptors. Neuroreport. 1996 Feb 2/29/1996; 7(3): 697-700. PMID: 8733724, ISSN: 0959-4965.
Fuhrmann S, Kirsch M, Hofmann HD. Ciliary neurotrophic factor promotes chick photoreceptor development in vitro. Development. 1995 Aug; 121(8): 2695-706. PMID: 7671829, ISSN: 0950-1991.
Fuhrmann Sabine, Overmann Joerg, Pfennig Norbert, Fischer Ulrich, et al. Influence of vitamin B12 and light on the formation of chlorosomes in green- and brown-colored Chlorobium species. Arch Microbiol. 1993; 160: 193-8.
Yang YP, Ma H, Starchenko A, Huh WJ, Li W, Hickman FE, Zhang Q, Franklin JL, Mortlock DP, Fuhrmann S, Carter BD, Ihrie RA, Coffey RJ. A Chimeric Egfr Protein Reporter Mouse Reveals Egfr Localization and Trafficking In Vivo. Cell Rep. 2017 May 5/9/2017; 19(6): 1257-67. PMID: 28494873, PII: S2211-1247(17)30542-9, DOI: 10.1016/j.celrep.2017.04.048, ISSN: 2211-1247.
Alldredge A, Fuhrmann S. Loss of Axin2 Causes Ocular Defects During Mouse Eye Development. Invest. Ophthalmol. Vis. Sci. 2016 Oct 10/1/2016; 57(13): 5253-62. PMID: 27701636, PII: 2565724, DOI: 10.1167/iovs.15-18599, ISSN: 1552-5783.
Bankhead EJ, Colasanto MP, Dyorich KM, Jamrich M, Murtaugh LC, Fuhrmann S. Multiple requirements of the focal dermal hypoplasia gene porcupine during ocular morphogenesis. Am. J. Pathol [print-electronic]. 2015 Jan; 185(1): 197-213. PMID: 25451153, PMCID: PMC4278246, PII: S0002-9440(14)00540-9, DOI: 10.1016/j.ajpath.2014.09.002, ISSN: 1525-2191.
Fuhrmann S, Zou C, Levine EM. Retinal pigment epithelium development, plasticity, and tissue homeostasis. Exp. Eye Res [print-electronic]. 2014 Jun; 123: 141-50. PMID: 24060344, PMCID: PMC4087157, PII: S0014-4835(13)00269-8, DOI: 10.1016/j.exer.2013.09.003, ISSN: 1096-0007.
Kruse-Bend R, Rosenthal J, Quist TS, Veien ES, Fuhrmann S, Dorsky RI, Chien CB. Extraocular ectoderm triggers dorsal retinal fate during optic vesicle evagination in zebrafish. Dev. Biol [print-electronic]. 2012 Nov 11/1/2012; 371(1): 57-65. PMID: 22921921, PMCID: PMC3455121, PII: S0012-1606(12)00435-6, DOI: 10.1016/j.ydbio.2012.08.004, ISSN: 1095-564X.
Westenskow PD, McKean JB, Kubo F, Nakagawa S, Fuhrmann S. Ectopic Mitf in the embryonic chick retina by co-transfection of ß-catenin and Otx2. Invest. Ophthalmol. Vis. Sci [print-electronic]. 2010 Oct; 51(10): 5328-35. PMID: 20463321, PMCID: PMC3066625, PII: iovs.09-5015, DOI: 10.1167/iovs.09-5015, ISSN: 1552-5783.
Bassett EA, Williams T, Zacharias AL, Gage PJ, Fuhrmann S, West-Mays JA. AP-2alpha knockout mice exhibit optic cup patterning defects and failure of optic stalk morphogenesis. Hum. Mol. Genet [print-electronic]. 2010 May 5/1/2010; 19(9): 1791-804. PMID: 20150232, PMCID: PMC2850623, PII: ddq060, DOI: 10.1093/hmg/ddq060, ISSN: 1460-2083.
Fuhrmann S. Eye morphogenesis and patterning of the optic vesicle. Curr. Top. Dev. Biol. 2010; 93: 61-84. PMID: 20959163, PMCID: PMC2958684, PII: B978-0-12-385044-7.00003-5, DOI: 10.1016/B978-0-12-385044-7.00003-5, ISSN: 1557-8933.
Westenskow P, Piccolo S, Fuhrmann S. Beta-catenin controls differentiation of the retinal pigment epithelium in the mouse optic cup by regulating Mitf and Otx2 expression. Development [print-electronic]. 2009 Aug; 136(15): 2505-10. PMID: 19553286, PMCID: PMC2709060, PII: dev.032136, DOI: 10.1242/dev.032136, ISSN: 0950-1991.
Fuhrmann S, Riesenberg AN, Mathiesen AM, Brown EC, Vetter ML, Brown NL. Characterization of a transient TCF/LEF-responsive progenitor population in the embryonic mouse retina. Invest. Ophthalmol. Vis. Sci [print-electronic]. 2009 Jan; 50(1): 432-40. PMID: 18599572, PMCID: PMC2615067, PII: iovs.08-2270, DOI: 10.1167/iovs.08-2270, ISSN: 1552-5783.
Zhang J, Fuhrmann S, Vetter ML. A nonautonomous role for retinal frizzled-5 in regulating hyaloid vitreous vasculature development. Invest. Ophthalmol. Vis. Sci [print-electronic]. 2008 Dec; 49(12): 5561-7. PMID: 18791178, PMCID: PMC2679971, PII: iovs.08-2226, DOI: 10.1167/iovs.08-2226, ISSN: 1552-5783.
Burns CJ, Zhang J, Brown EC, Van Bibber AM, Van Es J, Clevers H, Ishikawa TO, Taketo MM, Vetter ML, Fuhrmann S. Investigation of Frizzled-5 during embryonic neural development in mouse. Dev. Dyn. 2008 Jun; 237(6): 1614-26. PMID: 18489003, PMCID: PMC2562763, DOI: 10.1002/dvdy.21565, ISSN: 1058-8388.
Fuhrmann S. Wnt signaling in eye organogenesis. Organogenesis. 2008 Apr; 4(2): 60-7. PMID: 19122781, PMCID: PMC2613311, ISSN: 1547-6278.
Levine Edward M, Fuhrmann Sabine. An update on the regulation of rod photoreceptor development. In: Ophthal Res Series. Visual Transduction and Non-visual light perception. 4. [place unknown: publisher unknown]; 2008. Review; p. 3-64.
Seydewitz V, Rothermel A, Fuhrmann S, Schneider A, DeGrip WJ, Layer PG, Hofmann HD. Expression of CNTF receptor-alpha in chick violet-sensitive cones with unique morphologic properties. Invest. Ophthalmol. Vis. Sci. 2004 Feb; 45(2): 655-61. PMID: 14744911, ISSN: 0146-0404.
Fuhrmann S, Stark MR, Heller S. Expression of Frizzled genes in the developing chick eye. Gene Expr. Patterns. 2003 Oct; 3(5): 659-62. PMID: 12972002, PII: S1567133X03001078, ISSN: 1567-133X.
Fuhrmann S, Grabosch K, Kirsch M, Hofmann HD. Distribution of CNTF receptor alpha protein in the central nervous system of the chick embryo. J. Comp. Neurol. 2003 Jun 6/16/2003; 461(1): 111-22. PMID: 12722108, DOI: 10.1002/cne.10701, ISSN: 0021-9967.
Fuhrmann S, Levine EM, Reh TA. Extraocular mesenchyme patterns the optic vesicle during early eye development in the embryonic chick. Development. 2000 Nov; 127(21): 4599-609. PMID: 11023863, ISSN: 0950-1991.
Levine EM, Fuhrmann S, Reh TA. Soluble factors and the development of rod photoreceptors. Cell. Mol. Life Sci. 2000 Feb; 57(2): 224-34. PMID: 10766019, PII: 10.1007/PL00000686, DOI: 10.1007/PL00000686, ISSN: 1420-682X.
Fuhrmann S, Chow L, Reh TA. Molecular control of cell diversification in the vertebrate retina. Results Probl Cell Differ. 2000; 31: 69-91. PMID: 10929402, ISSN: 0080-1844.
Fuhrmann S, Heller S, Rohrer H, Hofmann HD. A transient role for ciliary neurotrophic factor in chick photoreceptor development. J. Neurobiol. 1998 Dec; 37(4): 672-83. PMID: 9858267, PII: 10.1002/(SICI)1097-4695(199812)37:4<672::AID-NEU14>3.0.CO;2-1, ISSN: 0022-3034.
Fuhrmann S, Kirsch M, Heller S, Rohrer H, Hofmann HD. Differential regulation of ciliary neurotrophic factor receptor-alpha expression in all major neuronal cell classes during development of the chick retina. J. Comp. Neurol. 1998 Oct 10/19/1998; 400(2): 244-54. PMID: 9766402, PII: 10.1002/(SICI)1096-9861(19981019)400:2<244::AID-CNE6>3.0.CO;2-9, ISSN: 0021-9967.
Kirsch M, Schulz-Key S, Wiese A, Fuhrmann S, Hofmann H. Ciliary neurotrophic factor blocks rod photoreceptor differentiation from postmitotic precursor cells in vitro. Cell Tissue Res. 1998 Feb; 291(2): 207-16. PMID: 9426308, ISSN: 0302-766X.
Fuhrmann S, Kirsch M, Wewetzer K, Hofmann HD. Use of cell ELISA for the screening of neurotrophic activities on minor cell populations in retinal monolayer cultures. J. Neurosci. Methods. 1997 Aug 8/22/1997; 75(2): 199-205. PMID: 9288653, PII: S0165-0270(97)00073-3, ISSN: 0165-0270.
Kirsch M, Fuhrmann S, Wiese A, Hofmann HD. CNTF exerts opposite effects on in vitro development of rat and chick photoreceptors. Neuroreport. 1996 Feb 2/29/1996; 7(3): 697-700. PMID: 8733724, ISSN: 0959-4965.
Fuhrmann S, Kirsch M, Hofmann HD. Ciliary neurotrophic factor promotes chick photoreceptor development in vitro. Development. 1995 Aug; 121(8): 2695-706. PMID: 7671829, ISSN: 0950-1991.
Fuhrmann Sabine, Overmann Joerg, Pfennig Norbert, Fischer Ulrich, et al. Influence of vitamin B12 and light on the formation of chlorosomes in green- and brown-colored Chlorobium species. Arch Microbiol. 1993; 160: 193-8.