Spatiotemporal Localisation of Heparan Sulphate Proteoglycans throughout Mouse Lens Morphogenesis

Abstract

Heparan sulphate proteoglycans (HSPGs) consist of a core protein decorated with sulphated HS-glycosaminoglycan (GAG) chains. These negatively charged HS-GAG chains rely on the activity of PAPSS synthesising enzymes for their sulfation, which allows them to bind to and regulate the activity of many positively charged HS-binding proteins. HSPGs are found on the surfaces of cells and in the pericellular matrix, where they interact with various components of the cell microenvironment, including growth factors. By binding to and regulating ocular morphogens and growth factors, HSPGs are positioned to orchestrate growth factor-mediated signalling events that are essential for lens epithelial cell proliferation, migration, and lens fibre differentiation. Previous studies have shown that HS sulfation is essential for lens development. Moreover, each of the full-time HSPGs, differentiated by thirteen different core proteins, are differentially localised in a cell-type specific manner with regional differences in the postnatal rat lens. Here, the same thirteen HSPG-associated GAGs and core proteins as well as PAPSS2, are shown to be differentially regulated throughout murine lens development in a spatiotemporal manner. These findings suggest that HS-GAG sulfation is essential for growth factor-induced cellular processes during embryogenesis, and the unique and divergent localisation of different lens HSPG core proteins indicates that different HSPGs likely play specialized roles during lens induction and morphogenesis.

Clearing the light path: Proteoglycans and their important roles in the lens and cornea

“…Col18a1 null mice have basement membrane assembly defects in a number of ocular tissues 53 . While there are many reports regarding the presence of proteoglycans in the lens capsule, 24,44,54–58 knowledge of their specific functions is limited. Perlecan is the most thoroughly examined of the lens capsule proteoglycan components, 24,59,60 followed by Collagen XVIII (Col18a1) 54–56,61 .…”

“…While there are many reports regarding the presence of proteoglycans in the lens capsule, 24,44,54–58 knowledge of their specific functions is limited. Perlecan is the most thoroughly examined of the lens capsule proteoglycan components, 24,59,60 followed by Collagen XVIII (Col18a1) 54–56,61 . The colocalization of FGF‐2 with perlecan in the lens equatorial capsule has implicated this heparin sulfate proteoglycan in the role of presenting FGF‐2 to the cells of the lens equatorial epithelium 58 .…”

“…Proteoglycans that link directly to the cell surface, 75 including the transmembrane syndecans and the GPI‐anchored glypicans, have been shown be expressed in the lens 54,55,76 . These lens cell‐associated proteoglycans include syndecans 1–4 and glypicans 1–6, 55 each with development and differentiation‐state specific patterns of expression 54 .…”

Sweet but Challenging: Tackling the Complexity of GAGs with Engineered Tailor‐Made Biomaterials

“…[190] However and despite tremendous interest, the vast structural heterogeneity of GAGs and the lack of dedicated tools have constituted severe limitations in the structural and functional characterization of GAGs and GAG/protein interactions. [200] The most documented example illustrating the impact of specific GAG motifs on proteins is the role of Hep, which activates [174] Copyright 2023, MDPI. B) Toluidine Blue staining representing the density variation of sulfated GAGs in the growth plate of wild-type mice.…”

“…Adapted with permission. [ 174 ] Copyright 2023, MDPI. B) Toluidine Blue staining representing the density variation of sulfated GAGs in the growth plate of wild‐type mice.…”