Browsing by Author "Tao, Chenqi"

Now showing 1 - 4 of 4
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    Cell surface proteoglycans control astrocyte migration and retinal angiogenesis by regulating basement membrane assembly
    (2015-12-15) Tao, Chenqi; Zhang, Xin
    Elaborate vascularization of the retina is crucial for the development and functioning of the eye. The proper patterning of astrocytes is a key event preceding retinal angiogenesis by providing guidance cues for endothelial cells, yet how this is regulated still remains obscure. The dual function of proteoglycans in both extracellular matrix (ECM) composition and cell signal transduction suggests their potential in the regulation of astrocyte migration. The current study demonstrated that non-cell-autonomous regulation by neuroretina cell surface proteoglycan is crucial for PDGF-A regulated astrocyte migration. Ablation of glycosaminoglycan side chains of proteoglycans in neuroretina led to impaired astrocyte migration, incomplete retinal angiogenesis, and hyaloid vessel persistence. This is followed by severe photoreceptor degeneration as a result of reactive gliosis, which cannot be rescued by constitutively activated Kras signaling. Notably, inner limiting membrane (ILM), the basement membrane of the retina, was breached in proteoglycan-deficient retinae prior to the formation of astrocytic network. Herein we propose that cell surface proteoglycans are essential for the initial assembly of ILM, and this cannot be compensated by secreted ECM proteoglycans. In support of this, after removal of ILM in retinal explant by Collagenase digestion, establishment of a new ILM can be achieved by incubation with exogenous laminin-supplemented Matrigel. This basement membrane reconstitution failed, however, in proteoglycan-deficient retinae or in wild type samples digested with a combination of Heparinase and ChABC in addition to Collagenase. Taken together, our study reveals a novel function of neuroretinal cell surface proteoglycans in the initial assembly of basement membrane which subsequently serves as a permissive substratum necessary for astrocyte migration.
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    Development of astrocytes in the vertebrate eye
    (Wiley Blackwell (John Wiley & Sons), 2014-12) Tao, Chenqi; Zhang, Xin; Department of Medical & Molecular Genetics, IU School of Medicine
    Astrocytes represent the earliest glial population in the embryonic optic nerve, contributing critically to retinal angiogenesis and formation of brain-retinal-barrier. Despite of many developmental and clinical implications of astrocytes, answers to some of the most fundamental questions of this unique type of glial cells remain elusive. This review provides an overview of the current knowledge about the origination, proliferation, and differentiation of astrocytes, their journey from the optic nerve toward the neuroretina, and their involvement in physiological and pathological development of the visual system.
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    Frs2α and Shp2 signal independently of Gab to mediate FGF signaling in lens development
    (Company of Biologists, 2014-02-01) Li, Hongge; Tao, Chenqi; Cai, Zhigang; Hertzler-Schaefer, Kristina; Collins, Tamica N.; Wang, Fen; Feng, Gen-Sheng; Gotoh, Noriko; Zhang, Xin; Department of Medical and Molecular Genetics, IU School of Medicine
    Fibroblast growth factor (FGF) signaling requires a plethora of adaptor proteins to elicit downstream responses, but the functional significances of these docking proteins remain controversial. In this study, we used lens development as a model to investigate Frs2α and its structurally related scaffolding proteins, Gab1 and Gab2, in FGF signaling. We show that genetic ablation of Frs2α alone has a modest effect, but additional deletion of tyrosine phosphatase Shp2 causes a complete arrest of lens vesicle development. Biochemical evidence suggests that this Frs2α-Shp2 synergy reflects their epistatic relationship in the FGF signaling cascade, as opposed to compensatory or parallel functions of these two proteins. Genetic interaction experiments further demonstrate that direct binding of Shp2 to Frs2α is necessary for activation of ERK signaling, whereas constitutive activation of either Shp2 or Kras signaling can compensate for the absence of Frs2α in lens development. By contrast, knockout of Gab1 and Gab2 failed to disrupt FGF signaling in vitro and lens development in vivo. These results establish the Frs2α-Shp2 complex as the key mediator of FGF signaling in lens development.
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    Lacrimal gland budding requires PI3K-dependent suppression of EGF signaling
    (American Association for the Advancement of Science, 2021-06-30) Wang, Qian; Tao, Chenqi; Hannan, Abdul; Yoon, Sungtae; Min, Xuanyu; Peregrin, John; Qu, Xiuxia; Li, Hongge; Yu, Honglian; Zhao, Jean; Zhang, Xin; Surgery, School of Medicine
    The patterning of epithelial buds is determined by the underlying signaling network. Here, we study the cross-talk between phosphoinositide 3-kinase (PI3K) and Ras signaling during lacrimal gland budding morphogenesis. Our results show that PI3K is activated by both the p85-mediated insulin-like growth factor (IGF) and Ras-mediated fibroblast growth factor (FGF) signaling. On the other hand, PI3K also promotes extracellular signal-regulated kinase (ERK) signaling via a direct interaction with Ras. Both PI3K and ERK are upstream regulators of mammalian target of rapamycin (mTOR), and, together, they prevent expansion of epidermal growth factor (EGF) receptor expression from the lacrimal gland stalk to the bud region. We further show that this suppression of EGF signaling is necessary for induction of lacrimal gland buds. These results reveal that the interplay between PI3K, mitogen-activated protein kinase, and mTOR mediates the cross-talk among FGF, IGF, and EGF signaling in support of lacrimal gland development.