Project
Investigating the role of calcium in the branching process of the chorioallantoic placenta
The placenta is a transient organ mediating maternal-fetal nutrient exchange, and therefore arbitrates developmental outcomes and fetal growth. A large exchange area is created by extensive branching morphogenesis of the trophoblasts to create a villous network, called labyrinth in mice. Pivotal to labyrinth formation is the differentiation and branching of Syncytiumtrophoblast layer II (SynTII). Our unpublished results demonstrated an essential role of calcium signaling through Transient Receptor Potential Vanilloid 2 (TRPV2) in SynTII cells as Trpv2-/- mice display fetal growth restriction and lethality, caused by impaired labyrinth structure. Trpv2 is abundantly expressed during SynTII differentiation, and its absence results in compromised labyrinth lineage specification. Here, we aim to investigate the role of calcium in cellular signaling during trophoblast branching. First, the effect of calcium through TRPV2 on the differentiation potential of SynTII will be assessed using single nucleus RNAseq. SynTII specific Trpv2-/- mice will help unravel whether defects are cell-autonomous. Then, the effect of attractant hormones on calcium signaling and SynTII migration will be evaluated. Finally, the role of calcium in human syncytialization will be identified by creating Crispr/cas9 mediated TRPV2-KO in human trophoblasts. This research tackles an important, currently understudied topic regarding calcium signals during placentation and will result in important breakthroughs.