Mericko, P. | bioRxiv Science

bioRxiv2024

YAP/TAZ signaling in allantois-derived cells is required for placental vascularization

Normal placental development and angiogenesis are crucial for fetal growth and maternal health during pregnancy. However, molecular regulation of placental angiogenesis has been difficult to study due to a lack of specific genetic tools that isolate the placenta from the embryo and yolk sac. To address this gap in knowledge we recently developed Hoxa13Cre mice in which Cre is expressed in allantois-derived cells, including placental endothelial and stromal cells. Mice lacking the transcriptional regulators Yes-associated protein (YAP) and PDZ-binding motif (TAZ) in allantois-derived cells exhibit embryonic lethality at midgestation with compromised placental vasculature. snRNA-seq analysis revealed transcriptional changes in placental stromal cells and endothelial cells. YAP/TAZ mutants exhibited significantly reduced placental stromal cells prior to the endothelial architectural change, highlighting the role of these cells in placental vascular growth. These results reveal a central role for YAP/TAZ signaling during placental vascular growth and implicate Hoxa13-derived placental stromal cells as a critical component of placental vascularization.

developmental biology↗

bioRxiv2022

Vascular mimicry by VE-cadherin enables trophoblast endovascular invasion and spiral artery remodeling during placental development

During formation of the mammalian placenta trophoblasts invade the maternal decidua and remodel spiral arteries to bring maternal blood into the placenta. This process, known as endovascular invasion, is thought to involve the adoption of functional characteristics of vascular endothelial cells (ECs) by trophoblasts through a process termed vascular mimicry. The genetic and molecular basis of vascular mimicry remains poorly defined, however, and whether trophoblasts utilize specialized endothelial proteins in an analogous manner to create vascular channels remains untested. Vascular endothelial (VE-)cadherin is a homotypic adhesion protein that is expressed selectively by ECs in which it enables formation of tight vessels and regulation of EC junctions. VE-cadherin is also expressed in invasive trophoblasts and is a prime candidate for a molecular mechanism of vascular mimicry by those cells. Here, we show that the VE-cadherin is required for trophoblast migration and endovascular invasion into the maternal decidua in the mouse. VE-cadherin deficiency results in loss of spiral artery remodeling that leads to decreased flow of maternal blood into the placenta, fetal growth restriction, and death. These studies identify a non-endothelial role for VE-cadherin in trophoblasts during placental development and suggest that endothelial proteins may play functionally unique roles in trophoblasts that do not simply mimic those in ECs.

developmental biology↗