EMAIL THIS PAGE TO A FRIEND

Endocrinology

Wnt-dependent T-cell factor-4 controls human etravillous trophoblast motility.


PMID 24605829

Abstract

Formation of migratory extravillous trophoblasts (EVTs) is critical for human placentation and hence embryonic development. However, key regulatory growth factors, hormones, and nuclear proteins controlling the particular differentiation process remain poorly understood. Here, the role of the Wingless (Wnt)-dependent transcription factor T-cell factor-4 (TCF-4) in proliferation and motility was investigated using different trophoblast cell models. Immunofluorescence of first-trimester placental tissues revealed induction of TCF-4 and nuclear recruitment of its coactivator β-catenin in nonproliferating EVTs, whereas membrane-associated β-catenin decreased upon differentiation. In addition, EVTs expressed the TCF-4/β-catenin coactivator Pygopus 2 as well as repressors of the Groucho/transducin-like enhancer of split family. Western blotting revealed Pygopus 2 expression and up-regulation of integrin α1 and nuclear TCF-4 in purified first-trimester cytotrophoblasts (CTBs) differentiating on fibronectin. Concomitantly, elevated TCF-4 mRNA, quantitated by real-time PCR, and increased TCF-dependent luciferase reporter activity were noticed in EVTs of villous explant cultures and differentiated primary CTBs. Gene silencing using specific small interfering RNA decreased TCF-4 transcript and protein levels, TCF-dependent reporter activity as well as basal and Wnt3a-stimulated migration of trophoblastic SGHPL-5 cells and primary CTBs through fibronectin-coated transwells. In contrast, proliferation of SGHPL-5 cells and primary cells, measured by cumulative cell numbers and 5-bromo-2'-deoxy-uridine labeling, respectively, was not affected. Moreover, siRNA-mediated down-regulation of TCF-4 in primary CTBs diminished markers of the differentiated EVT, such as integrin α1 and α5, Snail1, and Notch2. In summary, the data suggest that Wnt/TCF-4-dependent signaling could play a role in EVT differentiation promoting motility and expression of promigratory genes.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

SAB2104809
Anti-EGF antibody produced in rabbit, affinity isolated antibody, lyophilized powder
B3773 Anti-Human IgG (Fc specific)−Biotin antibody, Mouse monoclonal, clone HP-6017, purified from hybridoma cell culture
SAB1406069
Anti-KRT7 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
HPA007272
Anti-KRT7 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB2101306
Anti-KRT7 antibody produced in rabbit, affinity isolated antibody
SAB1410740
Anti-KRT7 antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
B5283 Anti-Rabbit IgG (γ-chain specific)−Biotin antibody, Mouse monoclonal, clone RG-96, purified from hybridoma cell culture
R2655
Anti-Rabbit IgG, Native antibody, Mouse monoclonal, clone RabT-50, purified from hybridoma cell culture
WH0001950M1
Monoclonal Anti-EGF antibody produced in mouse, clone 2F1, purified immunoglobulin, buffered aqueous solution
SAB5300488
Monoclonal Anti-EGF antibody produced in mouse, clone 9D7F11, ascites fluid
SAB5300489
Monoclonal Anti-EGF antibody produced in mouse, clone 4E11, ascites fluid
E2520 Monoclonal Anti-Epidermal Growth Factor antibody produced in mouse, clone EGF-10, purified immunoglobulin, buffered aqueous solution
G2904 Monoclonal Anti-Goat/Sheep IgG antibody produced in mouse, clone GT-34, ascites fluid
A8062 Monoclonal Anti-Goat/Sheep IgG–Alkaline Phosphatase antibody produced in mouse, clone GT-34, purified immunoglobulin, buffered aqueous glycerol solution
B3148 Monoclonal Anti-Goat/Sheep IgG–Biotin antibody produced in mouse, clone GT-34, purified immunoglobulin, buffered aqueous solution
F4891 Monoclonal Anti-Goat/Sheep IgG−FITC antibody produced in mouse, clone GT-34, purified immunoglobulin, buffered aqueous solution
A9452 Monoclonal Anti-Goat/Sheep IgG–Peroxidase antibody produced in mouse, clone GT-34, purified immunoglobulin, lyophilized powder
I6135 Monoclonal Anti-Human IgG (Fab specific) antibody produced in mouse, clone GG-6, ascites fluid
I6260 Monoclonal Anti-Human IgG (Fc specific) antibody produced in mouse, clone GG-7, ascites fluid
I6760 Monoclonal Anti-Human IgG (Fc specific) antibody produced in mouse, clone HP-6017, ascites fluid
F5016 Monoclonal Anti-Human IgG (Fc specific)−FITC antibody produced in mouse, clone HP-6017, purified immunoglobulin, buffered aqueous solution
I5885 Monoclonal Anti-Human IgG (γ-chain specific) antibody produced in mouse, clone GG-5, ascites fluid
I9513 Monoclonal Anti-Human IgG2 (Fc specific) antibody produced in mouse, clone HP-6002, ascites fluid
I9888 Monoclonal Anti-Human IgG4 (pFc′ specific) antibody produced in mouse, clone HP-6023, ascites fluid
R1008 Monoclonal Anti-Rabbit IgG (γ-chain specific) antibody produced in mouse, clone RG-96, ascites fluid
R3155 Monoclonal Anti-Rabbit IgG, Native−Peroxidase antibody produced in mouse, clone RabT-50, purified from hybridoma cell culture
R0761 Monoclonal Anti-Rat IgG2a antibody produced in mouse, clone R2A-2, ascites fluid