Sabine Fuhrmann

Associate Professor, Vanderbilt Eye Institute, Ophthalmology and Visual Sciences

B-3222 Medical Center North II

Nashville, TN 37232
(615) 936-0621


Cellular and molecular mechanisms regulating vertebrate eye patterning/differentiation and regeneration.

M.S. Biology, Carl von Ossietzky University, Oldenburg, Germany
Ph.D. Neurobiology, Albert Ludwigs University, Freiburg, Germany
Postdoc Developmental Biology, University of Washington, Seattle, USA

Research Description

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 dis­ruptions 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.

Postdoctoral positions: available

 

                 Porcn_fig_Furhmann.jpg

Figure Description: The acyltransferase Porcn is required for posttranslational modification and secretion of Wnt ligands. Conditional inactivation of Porcn induces several ocular defects in eye morphogenesis and retinal pigment epithelium (RPE) development. Porcn mutant eyes exhibit a closure defect of the ventral optic cup (coloboma, arrowhead in B) as well as pigment abnormalities (arrow). In coronal cryostat sections of Porcn mutant eyes, expression of Otx2 and Vsx2 in the retina appears normal, however, Vsx2 and Otx2 expression are ectopically upregulated in the dorsal and ventral RPE (arrow and arrowhead, respectively), indicating transdifferentiation of the RPE into neural retina.

 

 

 

 

 

Selected Publications​​

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 (2017). Generation of a Chimeric Egfr Protein Reporter Mouse Reveals Novel Aspects of Egfr Expression and Trafficking in Vivo. Cell Reports 19: 1257-1267. 

Alldredge A, Fuhrmann S. (2016). Loss of Axin2 causes ocular defects during mouse eye development. IOVS, 57: 5253-5262.

Bankhead EJ, Colasanto MP, Dyorich KM, Jamrich M, Murtaugh LC, Fuhrmann S. (2015). Multiple requirements of the Focal Dermal Hypoplasia gene Porcupine during ocular morphogenesis. Am J Pathol 185: 197-213.

Fuhrmann S, Zou C, Levine EM (2014). Retinal pigment epithelium development, plasticity, and tissue homeostasis. Exp Eye Res 123: 141-150.

Kruse-Bend R, Rosenthal J, Quist TS, Veien ES, Fuhrmann S, Dorsky RI, Chien CB (2012). Extraocular ectoderm triggers dorsal retinal fate during optic vesicle evagination in zebrafish. Dev Biol 371, 57-65.

Fuhrmann S (2010). Eye morphogenesis and patterning of the optic vesicle. Current Topics in Developmental Biology. Invertebrate and Vertebrate Eye Development. Cagan RL and Reh TA (eds.), Elsevier, Academic Press. Vol 93: 61-84.

Bassett EA, Williams T, Zacharias AL, Gage PJ, Fuhrmann S, West-Mays JA (2010). AP-2α Knockout Mice Exhibit Optic Cup Patterning Defects and Failure of Optic Stalk Morphogenesis. Hum Mol Genetics 19(9): 1791-1804.

Westenskow PD, McKean JB, Kubo K, Nagakawa S, Fuhrmann S (2010). Ectopic Mitf in the embryonic chicken retina by co-transfection of beta-catenin and Otx2. IOVS 51: 5328-5335. 

Fuhrmann S, Riesenberg A, Mathiesen AM, Brown EC, Vetter ML, Brown NL (2009). Characterization of a transient TCF/LEF-responsive progenitor population in the embryonic mouse retina. IOVS 50(1): 432-440. PMCID: PMC2615067.

Westenskow P, Piccolo S, Fuhrmann S (2009). Beta-catenin controls differentiation of the retinal pigment epithelium in the embryonic mouse optic cup by regulating Mitf and Otx2 expression. Development 136: 2505-2510.

Burns CJ, Zhang J, Brown EC, Van Bibber AM, Van Es J, Clevers H, Ishikawa T, Taketo MM, Vetter ML, Fuhrmann S (2008). Investigation of Frizzled-5 during embryonic neural development in mouse. Dev Dyn 237: 1614-1626. 

Fuhrmann S (2008). Wnt signaling in eye organogenesis. Organogenesis 4(2): 60-67. 

Zhang J, Fuhrmann S, Vetter ML (2008). A non-autonomous role for retinal Frizzled-5 in regulating hyaloid vitreous vasculature development. IOVS 49(12): 5561-5567. 

Levine EM, Fuhrmann S (2008). An update on the regulation of rod photoreceptor development. Ophthal Res Series. Visual Transduction and Non-visual light perception Vol 4: 3-64. (book chapter)