The Xenopus Tgfbi is required for embryogenesis through regulation of canonical Wnt signalling

Abstract

Tgfbi, a fasciclin family extracellular matrix protein, has various roles in human diseases from corneal dystrophies to cancer. However, the molecular mechanisms that underlie its functions are poorly understood. Here, we studied the role of Tgfbi during Xenopus embryogenesis. During gastrulation and immediately after, Xtgfbi is expressed at developmentally important signaling centers including the dorsal marginal zone, notochord and floorplate. Xtgfbi knockdown by anti-sense morpholinos causes defective organizer induction, patterning and differentiation of muscle, neuron and neural crests, similar to suppression of canonical Wnt signaling. In Xenopus embryos and animal caps as well as DLD-1 cells, we show that Tgfbi is strongly required for the full activation of the canonical Wnt pathway by promoting phosphorylation of GSK3β and consequently enhancing the stabilization and nuclear localization of β-catenin. Further analysis shows that Tgfbi is likely to promote GSK3β phosphorylation through integrin-linked kinase.

Transformation of the Transcriptomic Profile of Mouse Periocular Mesenchyme During Formation of the Embryonic Cornea

“…The absence of either collagens or regulatory proteoglycans causes dysfunctional fibrillogenesis and corneal opacity 10,132. Our results confirm a high expression of transcripts and upregulation of well-known corneal ECM proteins, including decorin, lumican, keratocan, and collagen I. Interestingly, several of the downregulated genes ( Vtn , Vcan , Has2 , and Tgfbi ) are involved in neural crest induction and migration 133–137. Several matricellular genes are upregulated at E14.5 and downregulated at E16.5 ( Fbln2 , Spp1 , and Ecm1 ), suggesting that they are required for cell migration, differentiation, or the initial organization of the corneal ECM.…”

Time-resolved quantitative proteomic analysis of the developing Xenopus otic vesicle reveals putative congenital hearing loss candidates

“…Together these findings indicate that Tgfbi is likely a direct target of Six1 in the developing inner ear. Third, tgfbi mRNA is expressed in the Xenopus larval OV 44 (confirmed by us, Figure 6 B). Fourth, Tgfbi is secreted into the perilymph of the human inner ear.…”

Identification of Prognostic Biomarkers by Combined mRNA and miRNA Expression Microarray Analysis in Pancreatic Cancer

“…Finally, TGFBI, also known as βig-H3, is a protein inducible by TGFβ1 and secreted by many cell types [60] . Furthermore, TGFBI is an important component of the Wnt signaling pathway [61] . It is located at 5q31.1.…”