ectoderm/extraembryonic ectoderm in the peri-implantation embryos, have the capacity to self-renew in the presence of FGF4 and mouse embryonic fibroblasts (MEFs). Using an in vitro system of embryonic stem (ES) cells, we have reported that the trophoblast lineage can be specified by activation of Cdx2. During differentiation, cells can adopt stem cell fate in the presence of FGF4/MEFs, otherwis...

BACKGROUND Impaired wound healing in diabetes is related to decreased production of growth factors. Hence, gene therapy is considered as promising treatment modality. So far, efforts concentrated on single gene therapy with particular emphasis on vascular endothelial growth factor-A (VEGF-A). However, as multiple proteins are involved in this process it is rational to test new approaches. There...

BACKGROUND The angiogenic response to myocardial ischemia can be augmented in animal models by gene transfer with the use of a replication defective adenovirus (Ad) containing a human fibroblast growth factor (FGF) gene. METHODS AND RESULTS The objectives of the Angiogenic GENe Therapy (AGENT) trial were to evaluate the safety and anti-ischemic effects of 5 ascending doses of Ad5-FGF4 in pati...

The inner cell mass (ICM) of the mammalian blastocyst contains pluripotent epiblast (EPI) and differentiating primitive endoderm (PE) cells, intermingled like salt and pepper. In mouse, the earliest known driver of EPI and PE cell fates is FGF4, but it was unclear whether cellular or molecular heterogeneity existed upstream of Fgf4. In a new study, published in the journal Nature Cell Biology, ...

Fibroblast growth factor 4 (Fgf4) has been implicated as a regulator of mesoderm formation, posteriorisation, neural induction and neural patterning. Much of the evidence for this derives from studies in which exogenous FGF4 is applied to avian embryos. We have therefore examined expression of endogenous Fgf4 mRNA in the developing chick embryo at stages when these processes are occurring. Expr...

The inner cell mass (ICM) of the mammalian blastocyst contains pluripotent epiblast (EPI) and differentiating primitive endoderm (PE) cells, intermingled like salt and pepper. In mouse, the earliest known driver of EPI and PE cell fates is FGF4, but it was unclear whether cellular or molecular heterogeneity existed upstream of Fgf4. In a new study, published in the journal Nature Cell Biology, ...

The emergence of pluripotent epiblast (EPI) and primitive endoderm (PrE) lineages within the inner cell mass (ICM) of the mouse blastocyst involves initial co-expression of lineage-associated markers followed by mutual exclusion and salt-and-pepper distribution of lineage-biased cells. Precisely how EPI and PrE cell fate commitment occurs is not entirely clear; however, previous studies in mice...

We previously established trophoblast stem cells from mouse androgenetic embryos (AGTS cells). In this study, to further characterize AGTS cells, we compared cell proliferation activity between trophoblast stem (TS) cells and AGTS cells under fibroblast growth factor 4 (FGF4) signaling. TS cells continued to proliferate and maintained mitotic cell division in the presence of FGF4. After FGF4 de...

Mouse embryonic stem cells (ESCs) differentiate into multiple cell types during organismal development. Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). The FGF4-MEK-ERK1/2 pathway is...

BACKGROUND Retinoic acid (RA) and fibroblast growth factor 4 (FGF4) signaling control endoderm patterning and pancreas induction/expansion. Based on these findings, RA and FGFs, excluding FGF4, have frequently been used in differentiation protocols to direct differentiation of hESCs into endodermal and pancreatic cell types. In vivo, these signaling pathways act in a temporal and concentration-...