Dawn of the organoid era: 3D tissue and organ cultures revolutionize the study of development, disease, and regeneration.

Novel and updated approaches of culturing cells in 3D are rapidly advancing our understanding of development, health, and disease. As tissues have been found to behave more realistically in 3D than in 2D cultures, organoid technology in combination with recent advances in the isolation and generation of stem cells, has rapidly become a promising concept in developmental and regenerative research. The development of all kinds of tissues can now be studied "in a dish," allowing more detailed observations of stem cell maintenance, morphogens, and differentiation.

Twenty one years of P19 cells: what an embryonal carcinoma cell line taught us about cardiomyocyte differentiation.

Many different stem cell types have been shown to differentiate into cardiac muscle cells in vitro but P19 embryonal carcinoma (EC) cells were one of the first examples described and have been the most extensively characterized. P19 EC cells, isolated from an experimental embryo-derived teratocarcinoma in mice, are multipotent and can differentiate into cell types of all three germ layers. Because of their capacity to form cardiomyocytes however, they have been used to dissect the role of cardiac-specific transcription factors and upstream signalling pathways in cardiac cell differentiation.

The defective transforming phenotype of c-Jun Ala(63/73) is rescued by mutation of the C-terminal phosphorylation site.

Cotransfection of primary rat embryo fibroblasts (REF) with c-Jun and activated Ras leads to oncogenic transformation and this process requires the phosphorylation of the N-terminal domain of c-Jun. Ras augments this phosphorylation and, consequently activates the c-Jun transactivation property of TRE (TPA Responsive Element)-dependent promoters. To analyse the role of the c-Jun C-terminal phosphorylation site in oncogenic cooperation we tested the activities of N-terminal c-Jun Ala(63/73) (named Nt), C-terminal c-Jun Ala(234/242/246/252) (named Ct) and (Nt+Ct)-with both mutations-non-phosphorylatable c-Jun mutants.

Cloning and analysis of the mouse follistatin promoter.

Follistatin is a secreted protein, which functions as an antagonist of different members of the TGF-beta superfamily, including activin and bone morphogenetic proteins. Expression of follistatin is tightly regulated during mouse development both spatially and temporally. In order to study the regulation of follistatin expression in the mouse embryo we have cloned and analyzed part of the 5' flanking region of the murine follistatin gene.

Snail is an immediate early target gene of parathyroid hormone related peptide signaling in parietal endoderm formation.

In mouse development, parietal endoderm (PE) is formed from both primitive endoderm (PrE) and visceral endoderm (VE). This process can be mimicked in vitro by using F9 embryonal carcinoma cells (EC) cells, differentiated to PrE or VE cells, and treating these with Parathyroid Hormone related Peptide (PTHrP). By means of differential display RT-PCR, we identified Snail (Sna) as a gene upregulated during the differentiation from F9 PrE to PE.