THE ROLE OF FRS2α IN LENS DEVELOPMENT
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Miami University / OhioLINK
2012
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ndltd-OhioLink-oai-etd.ohiolink.edu-miami13534208182021-08-03T05:41:42Z THE ROLE OF FRS2α IN LENS DEVELOPMENT Bhavani, Madakashira P. Developmental Biology Genetics Molecular Biology ocular lens Frs2&945 development mouse genetics For more than a century, the lens has provided an excellent model to elucidate the basic processes of induction, differentiation, cell cycle exit and cell survival mechanisms. The lens is composed of a single layer of proliferative epithelial cells in the anterior hemisphere and the bulk of the lens is composed of post- mitotic fiber cells that are continually differentiated from the epithelial cells at the lens equator. Lens epithelial cells express numerous receptor tyrosine kinases with the ability to initiate cell signaling ultimately leading to the phosphorylation (activation) of Erk1/2 and PI3-K/Akt signaling. However, only the over- expression of Fgfs in the lens leads to premature fiber cell differentiation of the epithelial cells in transgenic mice (characterized by expression of β crystallins), and the lens specific loss of Fgfrs lead to abrogation of fiber cell differentiation, and extensive cell death. A variety of signaling proteins are phosphorylated in response to Fgf stimulation, including Shc, phospholipase-Cγ, STAT1, Gab1 and docking molecules Frs2α and Frs2β. We have shown that Frs2β is not expressed in the murine lens, and within the lens, only Fgfrs tyrosine phosphorylate and activate Frs2α. In mice, the lens specific loss of Frs2α significantly increases apoptosis and decreases phosphorylation of both Erk1/2 and Akt, decreases cell survival, fiber cell elongation and fiber cell differentiation. Although not normally expressed in the lens, the receptor TrkC tyrosine phosphorylates Frs2α upon stimulation by NT3. Transgenic mice expressing TrkC and NT3 in the lens exhibit increased Erk1/2 and Akt activation as well as the elongation and the expression of β-crystallins in the lens epithelium that remains entirely dependent on Frs2α activation. 2012-11-26 English text Miami University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=miami1353420818 http://rave.ohiolink.edu/etdc/view?acc_num=miami1353420818 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
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NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Developmental Biology Genetics Molecular Biology ocular lens Frs2&945 development mouse genetics |
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Developmental Biology Genetics Molecular Biology ocular lens Frs2&945 development mouse genetics Bhavani, Madakashira P. THE ROLE OF FRS2α IN LENS DEVELOPMENT |
| author |
Bhavani, Madakashira P. |
| author_facet |
Bhavani, Madakashira P. |
| author_sort |
Bhavani, Madakashira P. |
| title |
THE ROLE OF FRS2α IN LENS DEVELOPMENT |
| title_short |
THE ROLE OF FRS2α IN LENS DEVELOPMENT |
| title_full |
THE ROLE OF FRS2α IN LENS DEVELOPMENT |
| title_fullStr |
THE ROLE OF FRS2α IN LENS DEVELOPMENT |
| title_full_unstemmed |
THE ROLE OF FRS2α IN LENS DEVELOPMENT |
| title_sort |
role of frs2α in lens development |
| publisher |
Miami University / OhioLINK |
| publishDate |
2012 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=miami1353420818 |
| work_keys_str_mv |
AT bhavanimadakashirap theroleoffrs2ainlensdevelopment AT bhavanimadakashirap roleoffrs2ainlensdevelopment |
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1719423737950896128 |