During a process called gastrulation, pluripotent stem cells forming the tissue known as the epiblast differentiate to form the three somatic germ layers (endoderm, mesoderm, and ectoderm). Spatial organization and axis formation are critical during this early embryonic developmental period, with which the extracellular signaling molecule BMP4 has been known for many years to be critically involved.

In this study, the research team found that tight junctions--a type of intercellular adhesion complexes--specify sensitivity toward BMP4 in an iPS cell-derived differentiation model using that recapitulates the process of gastrulation of human embryos. They identified TJP1 as a critical factor that helps set up the molecular barrier defining the apical and basolateral polarity of the cells in the early embryo. Notably, they observed TJP1 knockdown results in ubiquitous and sustained activation of intracellular signaling pathways downstream of BMP4 and ushers the genetically modified pluripotent stem cell colonies toward a cell fate known as primordial germ cell-like cell (PGCLC), which are precursors of human sperm and egg cells. Thus, by illuminating the molecular details of how tight junctions created with TJP1 affect BMP4 signaling, the researchers have discovered a novel way to effectively produce PGCLCs that may be used one day to generate eggs for in vitro fertilization to help treat female infertility.

The results of this research are featured in a news article from the Gladstone Institutes.

• A Key Function for Tight Junctions in Embryo Models (the Gladstone Institutes)

The results of this study were published in Developmental Cell on June 23, 2023.

• doi: 10.1016/j.devcel.2023.05.019