Abstract
CCN2/CTGF is a matricellular protein that is known to enhance transforming growth factor-β signaling and to induce a myofibroblast-like phenotype in a variety of cell types. Here, we investigated Ccn2/Ctgf promotor activity during development and in the adult mouse eye, using CTGFLacZ/+ mice in which the β-galactosidase reporter gene LacZ had been inserted into the open reading frame of Ccn2/Ctgf. Promotor activity was assessed by staining for β-galactosidase activity and by immunolabeling using antibodies against β-galactosidase. Co-immunostaining using antibodies against glutamine synthetase, glial fibrillary acidic protein, choline acetyltransferase, and CD31 was applied to identify specific cell types. Ccn2/Ctgf promotor activity was intense in neural crest-derived cells differentiating to corneal stroma and endothelium, and to the stroma of choroid, iris, ciliary body, and the trabecular meshwork during development. In the adult eye, a persistent and very strong promotor activity was present in the trabecular meshwork outflow pathways. In addition, endothelial cells of Schlemm’s canal, and of retinal and choroidal vessels, retinal astrocytes, Müller glia, and starburst amacrine cells were stained. Very strong promoter activity was seen in the astrocytes of the glial lamina at the optic nerve head. We conclude that CCN2/CTGF signaling is involved in the processes that govern neural crest morphogenesis during ocular development. In the adult eye, CCN2/CTGF likely plays an important role for the trabecular meshwork outflow pathways and the glial lamina of the optic nerve head.
Highlights
CCN2 is a member of the cellular communication network (CCN) family of extracellular matrix-associated and heparinbinding matricellular proteins (Brigstock 2003; Leask 2020; Perbal and Perbal 2016; Perbal 2013, 2018)
We conclude that CCN2/connective tissue growth factor (CTGF) signaling is involved in the processes that govern neural crest (NC) morphogenesis during late embryonic and postnatal eye development
This conclusion rests on our observation of (1) Ccn2/ Ctgf promoter activity in NC-derived cells differentiating to uveal and corneal tissues, and (2) persistent strong promoter activity in trabecular meshwork, endothelial cells of Schlemm’s canal, retinal and choroidal vessels, and astrocytes of the optic nerve head glial lamina
Summary
CCN2 is a member of the cellular communication network (CCN) family of extracellular matrix-associated and heparinbinding matricellular proteins (Brigstock 2003; Leask 2020; Perbal and Perbal 2016; Perbal 2013, 2018). It is more commonly known under its original name connective tissue growth factor (CTGF) that was recently discontinued by the HUGO Gene Nomenclature Committee which adopted the use of CCN2 instead (Perbal et al 2018). The domains consist of the insulin-like growth factor binding protein (IGFBP) domain, the von Willebrand. CCN2/CTGF is highly overexpressed in conditions associated with increased extracellular matrix (ECM) synthesis and fibrosis such as scleroderma (Sato et al 2000; Yamamoto et al 2005), diabetic nephropathy and kidney fibrosis (Mason 2013; Yin and Liu 2019), fibrotic liver
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