Project Details
Projekt
CCN3 (NOV): Key regulator promoting cell cycle exit and migration of trophoblast cells into the maternal compartment
Applicant
Professorin Dr. Alexandra Gellhaus
Subject Area
Reproductive Medicine, Urology
Term
from 2014 to 2018
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 246503793
Appropriate placentation relies on the capacity of first trimester EVT cells to proliferate and then to invade into the maternal tissue after having escaped from the cell cycle. Changes in this highly coordinated programme could lead to the pregnancy disease preeclampsia characterized by trophoblast hypoinvasion and defective vascular remodeling.We have shown that the matricellular protein CCN3 contributes to the regulation of the switch from the proliferating trophoblast of the cell column to the non-proliferating phenotype invading the decidua and the spiral arteries during placental development by causing a G0/G1 cell cycle arrest as well as enhancing migration properties. The cell cycle arrest is accompanied by an increased expression of activated Notch1 and its target gene p21. At the same time CCN3 increases migration properties of trophoblast cells by an activation of FAK and Akt pathways via integrins.In this proposed study we want to investigate more precisely the detailed molecular mechanisms how CCN3 regulates the G0/G1 cell cycle arrest and how the migration can be triggered at the same time to fulfil a successful placental development. Moreover, we would like to identify impaired signaling cascades mediated by CCN3 for proliferation and / or migration properties in early-onset preeclampsia.
DFG Programme
Research Grants
International Connection
Canada
