Tsukushi modulates Xnr2, FGF and BMP signaling: regulation of Xenopus germ layer formation.

PLoS One

Department of Oncology, The Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, United Kingdom.

Published: October 2007

Background: Cell-cell communication is essential in tissue patterning. In early amphibian development, mesoderm is formed in the blastula-stage embryo through inductive interactions in which vegetal cells act on overlying equatorial cells. Members of the TGF-beta family such as activin B, Vg1, derrière and Xenopus nodal-related proteins (Xnrs) are candidate mesoderm inducing factors, with further activity to induce endoderm of the vegetal region. TGF-beta-like ligands, including BMP, are also responsible for patterning of germ layers. In addition, FGF signaling is essential for mesoderm formation whereas FGF signal inhibition has been implicated in endoderm induction. Clearly, several signaling pathways are coordinated to produce an appropriate developmental output; although intracellular crosstalk is known to integrate multiple pathways, relatively little is known about extracellular coordination.

Methodology/principal Findings: Here, we show that Xenopus Tsukushi (X-TSK), a member of the secreted small leucine rich repeat proteoglycan (SLRP) family, is expressed in ectoderm, endoderm, and the organizer during early development. We have previously reported that X-TSK binds to and inhibits BMP signaling in cooperation with chordin. We now demonstrate two novel interactions: X-TSK binds to and inhibits signaling by FGF8b, in addition to binding to and enhancement of Xnr2 signaling. This signal integration by X-TSK at the extracellular level has an important role in germ layer formation and patterning. Vegetally localized X-TSK potentiates endoderm formation through coordination of BMP, FGF and Xnr2 signaling. In contrast, X-TSK inhibition of FGF-MAPK signaling blocks ventrolateral mesoderm formation, while BMP inhibition enhances organizer formation. These actions of X-TSK are reliant upon its expression in endoderm and dorsal mesoderm, with relative exclusion from ventrolateral mesoderm, in a pattern shaped by FGF signals.

Conclusions/significance: Based on our observations, we propose a novel mechanism by which X-TSK refines the field of positional information by integration of multiple pathways in the extracellular space.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1994590PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0001004PLOS

Publication Analysis

Top Keywords

signaling
8
bmp signaling
8
germ layer
8
layer formation
8
mesoderm formation
8
multiple pathways
8
pathways extracellular
8
x-tsk
8
x-tsk binds
8
binds inhibits
8

Similar Publications

Background: This study aimed to provide a comprehensive review of adverse events (AEs) associated with factor Xa (FXa) inhibitors in pediatric patients.

Methods: We searched PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and the European Union Clinical Trials Register for English-language records from the establishment of the database up to October 17, 2023.

View Article and Find Full Text PDF

TRPV4 as a Novel Regulator of Ferroptosis in Colon Adenocarcinoma: Implications for Prognosis and Therapeutic Targeting.

Dig Dis Sci

January 2025

Ningxia Medical University, Xing Qing Block, Shengli Street No.1160, Yin Chuan City, 750004, Ningxia Province, People's Republic of China.

Background: Colon adenocarcinoma (COAD) is a leading cause of cancer-related mortality worldwide. Transient receptor potential vanilloid 4 (TRPV4), a calcium-permeable non-selective cation channel, has been implicated in various cancers, including COAD. This study investigates the role of TRPV4 in colon adenocarcinoma and elucidates its potential mechanism via the ferroptosis pathway.

View Article and Find Full Text PDF

Introduction: Colorectal cancer (CRC) is the second most common cause of cancer-related deaths globally. The gut microbiota, along with adenomatous polyps (AP), has emerged as a plausible contributor to CRC progression. This study aimed to scrutinize the impact of the FadA antigen derived from Fusobacterium nucleatum on the expression levels of the ANXA2 ceRNA network and assess its relevance to CRC advancement.

View Article and Find Full Text PDF

The nutrient germinant receptors (GRs) in spores of Bacillus species consist of a cluster of three proteins- designated A, B, and C subunits- that play a critical role in initiating the germination of dormant spores in response to specific nutrient molecules. The Bacillus cereus GerI GR is essential for inosine-induced germination; however, the roles of the individual subunits and the mechanism by which germinant binding activates GR function remain unclear. In this study, we report the backbone chemical shift assignments of the N-terminal domain (NTD) of the A subunit of GerI (GerIA).

View Article and Find Full Text PDF

Objective: Rheumatoid arthritis (RA) is an autoimmune condition that causes severe joint deformities and impaired functionality, affecting the well-being and daily life of individuals. Consequently, there is a pressing demand for identifying viable therapeutic targets for treating RA. This study aimed to explore the molecular mechanisms of osteoclast differentiation in PBMC from patients with RA through transcriptome sequencing and bioinformatics analysis.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!