Role of Hippo signaling pathway in early placental development

Abstract

The placenta is an organ of fetal origin that develops at the interface with the maternal uterus (1). It performs numerous and diverse functions fundamental for the proper growth and development of the semiallogeneic fetus, including gas, nutrient, and waste exchange; production of hormones; and modulation of maternal immune response. Placental development begins, following implantation of the blastocyst-stage embryo, with the expansion of the trophectoderm (TE) and establishment of a villous trophoblast progenitor population, termed cytotrophoblast (CTB) (2). As this cell layer grows and invaginates to form chorionic villi (functional units of the human placenta), the CTB further expands and differentiates into two main mature trophoblast cell types: the syncytiotrophoblast (STB), involved in gas/nutrient exchange, and extravillous trophoblast (EVT), which invades the maternal decidua and remodels maternal spiral arterioles (Fig. 1). However, the mechanisms behind early events in human placentation, particularly CTB self-renewal and differentiation, are largely unknown. Using tools recently developed to study early human placental development, two studies in PNAS address the role of the Hippo pathway in trophoblast progenitor self-renewal. Both focus on the Hippo mediator complex containing TEAD4: Saha et al. (3) compare its function in early postimplantation mouse placenta with first-trimester human placenta and associate its deficiency with recurrent pregnancy loss (RPL), while Meinhardt et al. (4) focus on the mechanism by which its transcriptional cofactor yes-associated protein 1 (YAP1) regulates trophoblast stemness. Fig. 1. Human placental chorionic villus showing the different trophoblast subtypes: vCTB, STB, and EVTs in the maternal decidua, the … [↵][1]1To whom correspondence may be addressed. Email: mparast{at}ucsd.edu. [1]: #xref-corresp-1-1