Involvement of Tsukushi in diverse developmental processes

Abstract

Tsukushi (TSK) is a small signaling molecule which takes part in different developmental processes of multiple vertebrate organisms. The diverse activity of TSK depends on its ability to bind various intermediate molecules from different major signaling pathways. Interactions of TSK with BMP, FGF, TGF-β and Wnt pathways have already been confirmed. In this review, we will introduce the latest information regarding the involvement of TSK in developmental events. We suggest a fine tuning role for TSK in multiple signaling cascades. Also, we recommend further studies on the developmental role of TSK to fully reveal its potential.

The hepatokine Tsukushi is released in response to NAFLD and impacts cholesterol homeostasis

“…TSK-null animals were smaller compared with wild-type littermates (Supplemental Figure 5E). This phenotype was reported previously and is consistent with the established role of TSK in regulating development in mice (50,51). No differences in body weight gain were found between wild-type and TSK-null mice exposed to HFD (Supplemental Figure 5F).…”

“…Here, we show that hepatic TSK acutely modulates gene expression in the liver, indicating that TSK acts at least via an autocrine and/or paracrine mechanism. This supports previous literature showing that TSK is an extracellular protein that can locally affect the activity of several signaling pathways (51). Studies in chick and Xenopus showed that TSK controls BMP, Wnt, FGF, and TGF-β signaling during development and organogenesis by interacting with various soluble factors and receptors (51).…”

“…This supports previous literature showing that TSK is an extracellular protein that can locally affect the activity of several signaling pathways (51). Studies in chick and Xenopus showed that TSK controls BMP, Wnt, FGF, and TGF-β signaling during development and organogenesis by interacting with various soluble factors and receptors (51). The impact of TSK on these signaling cascades in adult tissues has never been investigated to our knowledge.…”

Tsukushi is essential for the development of the inner ear

“…Tsukushi (TSK) is a small, secreted leucine-rich-repeat proteoglycan and extracellular signaling molecule that participates in various developmental processes in vertebrates [1][2][3]. The diverse functions of TSK depend on its ability to bind and interact with various intermediate molecules of some major signaling pathways.…”

Tsukushi is essential for proper maintenance and terminal differentiation of mouse hippocampal neural stem cells

“…Tsukushi (TSK) is one such protein which belongs to Small Leucine‐Rich Proteoglycan (SLRP) family and has important regulatory roles in various developmental pathways. TSK directly binds to signaling pathway molecules and conserves the optimum output of multiple signaling pathways (Ahmad, Anam, Ito, & Ohta, ). The first evidence of TSK function was found during chick gastrulation, where TSK binds to BMP4 and Chordin to inhibit BMP signaling and thus induces the Hensen's node and primitive streak formation (Ohta et al, ).…”