Browsing by Author "Ravi, Vagisha"

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    Role of TGF-β Activated Kinase 1(TAK1) in Chick Retinal Development
    (Office of the Vice Chancellor for Research, 2014-04-11) Ravi, Vagisha; Belecky-Adams, Teri
    Bone morphogenetic proteins (BMPs) play a critical role in vertebrate eye development by regulating cell fate processes in the retina through canonical SMAD and non-canonical MAPK pathways. TGF-β Activated Kinase 1(TAK1) is a MAPKKK that activates the MAPK cascade upon BMP activation. Dysregulation of TAK1 is associated with a variety of diseased states including cancer, but little is known about the role of TAK1 in development. Recent in vitro studies have indicated that TAK1 inhibits the G1-S phase Cyclin D, a process known to be critical to cell cycle exit. Although no studies have focused on the role of TAK1 in retinal development, many studies have indicated that BMPs as well as properly timed cell cycle exit are critical for the differentiation of specific cell types. In studies designed to test the hypothesis that TAK1 is an essential regulator of cell cycle exit in the chick embryonic retina, we have performed immunohistochemistry using an antibody that specifically detects the activated form of TAK1 (pTAK1) and shown the extensive localization of pTAK1 in a subset of differentiated cells and, more prominently, in the mitotic progenitor cells of the retina. Our preliminary studies, aimed at in vivo pharmacological inhibition of TAK1 activity using (5Z)-7-Oxozeaenol in the developing chick eye, show that TAK1 inhibition could lead to a range of developmental defects in the retina. While further studies focusing on molecular changes resulting from TAK1 inhibition and overexpression would shed more light on its functional role in the retina, our results suggest that TAK1 signaling is critical for normal eye development. The heavy localization of pTAK1 in mitotic progenitor cells especially, could be indicative of its role in cell cycle exit. Understanding the functional role of this protein in the context of eye development could aid in understanding the pathophysiology of diseased states associated with TAK1.
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    TAK1 inhibition increases proliferation and differentiation of chick retinal cells
    (Frontiers Media, 2022-09-13) Carrillo, Casandra; Ravi, Vagisha; Tiwari, Sarika; Chernoff, Ellen A.; Belecky-Adams, Teri L.; Biology, School of Science
    The factors necessary for the differentiation of cell types within the retina are incompletely understood. The transforming growth factor beta (TGF-β) superfamily, including TGF-β1 and 2, the bone morphogenetic proteins, and the activins have all been implicated in differentiation; however, the mechanisms by which these factors affect differentiation are only partially understood. The studies herein focus on a potential role for transforming growth factor β-activated kinase 1 (TAK1), a hub kinase that lies at the intersection of multiple signaling pathways, in the differentiation of cell types within the chick retina. Previous studies have focused predominantly on the role this kinase plays in the inflammation process and axonal growth. TAK1 is downstream of multiple signaling pathways that are critical to development of the central nervous system, including transforming growth factor β (TGFβ), bone morphogenetic proteins (BMPs), and activins. The present study indicates that activated TAK1 is found throughout the developing retina; however, it is localized at higher levels in dividing and differentiating cells. Further, ex ovo retinal studies using TAK1 inhibitor 5Z-7-oxozeaenol increased both progenitor and differentiating cell populations, accompanied by a substantial increase in proliferation and a smaller increase in cell death. These results indicate a unique role for TAK1 in differentiating and proliferating retinal cells.