Dominant negative inhibition of canonical Notch signaling in trophoblast cells does not disrupt placenta formation
Open Access
- 1 January 2019
- journal article
- research article
- Published by The Company of Biologists in Biology Open
- Vol. 8 (4)
- https://doi.org/10.1242/bio.037721
Abstract
Proper development and function of the mammalian placenta requires interactions between embryo-derived trophoblasts and uterine endothelial cells to form mosaic vessels that facilitate blood flow to a developing conceptus. Notch signaling utilizes a cell–cell contact dependent mechanism to drive cell behaviors, such as differentiation and invasion. In mice, Notch2 is needed for proper placentation and embryo survival. We used transgenic mice with a dominant-negative form of Mastermind-like1 and Cyp19-Cre and Tpbpa-Cre drivers to inhibit canonical Notch signaling in trophoblasts. Both Cre drivers resulted in robust placental expression of dominant-negative Mastermind-like1. All pregnancies progressed beyond mid-gestation and morphological analyses of placentas revealed no differences between mutants and controls. Our data suggest that mouse placentation occurs normally despite dominant negative inhibition of trophoblast canonical Notch signaling and that Notch2 signaling via the canonical pathway is not necessary for placentation.Funding Information
- National Heart, Lung, and Blood Institute (1R01HL127013-01A1)
This publication has 39 references indexed in Scilit:
- Response gene to complement 32 deficiency causes impaired placental angiogenesis in miceCardiovascular Research, 2013
- Placental contribution to the origins of sexual dimorphism in health and diseases: sex chromosomes and epigeneticsBiology of Sex Differences, 2013
- Non-canonical Notch signaling: emerging role and mechanismTrends in Cell Biology, 2012
- Notch Signaling in Developmental and Tumor AngiogenesisGenes & Cancer, 2011
- A role for Notch signaling in trophoblast endovascular invasion and in the pathogenesis of pre-eclampsiaDevelopment, 2011
- Chapter 12 Placental Remodeling of the Uterine VasculatureMethods in Enzymology, 2008
- Expression of Cre recombinase in early diploid trophoblast cells of the mouse placentagenesis, 2007
- Structures of CSL, Notch and Mastermind proteins: piecing together an active transcription complexCurrent Opinion in Structural Biology, 2007
- Severe Feto-Placental Abnormalities Precede the Onset of Hypertension and Proteinuria in a Mouse Model of Preeclampsia1Biology of Reproduction, 2006
- Implantation and the placenta: key pieces of the development puzzleScience, 1994