Vasculature-related genes expressed in the allantois or placenta and their corresponding phenotypes in the mutant allantois or placenta
| Category/gene name . | Expression in the allantois or placenta . | Ref. . | Phenotype in allantois or placenta . | Ref. . | |
|---|---|---|---|---|---|
| Age . | Area of expression . | ||||
| Vegf signaling | |||||
| Vegf | E8.5, E12.5 | Mt, labyrinthine stroma | 19,20 | Degenerating endothelium in placenta | 21 |
| Flk1 | E7.5, E8.75, E12.5 | EC, placental vasculature | 5,19,20 | Lack of mature ECs in the allantois | 22 |
| Flt1 | E8.75, E12.5 | EC, placental vasculature | 5,19,20 | Nd | |
| EC | |||||
| Pecam | E8.0 onwards | EC | 5 | None (viable) | 23 |
| VE-Cad | E8.0 onwards | EC | 5 | No allantois plexus | 24-27 |
| Hematopoietic | |||||
| Tal1 | E7.0-8.0 | EPC | 5 | Absence of blood | 28 |
| Runx1 | E8.0-8.5 | Hematopoietic precursors | 7 | Nd | |
| SMC | |||||
| SM22α | E8.25 | SMC | None (viable) | 29 | |
| αSMA | E8.25 | SMC | Nd | ||
| ECM | |||||
| Fn | E8.25 | Mes* | 30 | Nd | |
| Itgα5 | E8.25 | Mes | 31 | Nd | |
| Collagen1α (I) | E8.25 | Mes | 31 | Nd | |
| Has2 | E8.25 | Mes | 31 | Nd | |
| Vcan | E8.25 | Mes | 31 | Nd | |
| Adamts9 | E7.5 | Mes | 32 | Nd | |
| Remodeling of vascular plexus | |||||
| Nrp1 | Nd | Nd | Nd | ||
| Nrp2 | Nd | Nd | Nd | ||
| Tie1 | E8.75, E12.5 | EC, placental vasculature | 19,20 | Nd | |
| Tie2 | E8.75, E12.5 | EC, placental vasculature | 19,20 | Nd | |
| Ang1 | Nd | Nd | Lack of complexity in umbilical vessels | 33 | |
| Ang2 | Nd | Nd | Nd | ||
| Tgfβ | E7.5-8.5 | Nd | 34 | Defective chorio-allantoic fusion; lack of Flk1 expression in allantois | 35 |
| Alk1 | Nd | Nd | Nd | ||
| Alk5 | Nd | EC and SMC of placenta | 36 | Defective sprouting of allantois into placenta; lack of SMCs around allantoic vessels | 36 |
| Edd | Nd | Nd | ECs fail to form plexus, lack of chorio-allantoic fusion | 37 | |
| Lpp3 | E8.0-E10.5 | Mes | 38 | ECs fail to form plexus, lack of chorio-allantoic fusion | 38 |
| Artery versus vein | |||||
| ephrinB2 | E9.5 | Vascular plexus, UA | 39 | None | 40 |
| EphrinB4 | E9.0 | EC/UV | 39 | Nd | |
| Notch2 | E8.25 | Mes | 31,41 | Nd | |
| Dll4 | E8.25 | Arterial EC | 31 | Degenerating vasculature in placenta | 42 |
| Jag1 | E8.25 | Mes | 31 | Nd | |
| Hey1 Hey2 | E8.5, E9.0 | Mes | 43 | Vasculature in CAP but not in the labyrinth | 44 |
| Signaling molecules | |||||
| Wnt2 | E8.0-9.5 | Mes | 45 | Late gestation hemorrhage; tissue disruption in placenta | 45 |
| Wnt5a | E7.0, 8.0 | Mes | 46 | No affect on allantois | 46 |
| Wnt11 | E7.0-8.0 | Mes | 47 | Nd | |
| Rspo3 | E8.0, 8.5 | Mes | 48 | Vessels fail to invade placenta | 48,49 |
| Bmp4 | E8.25 | Mes | 50 | Small or no allantois | 51 |
| Smad1 | E7.25 | Mes | 52 | No chorio-allantoic fusion | 52 |
| Transcription factors | |||||
| Etv2 | E7.5, E8.25 | Mes | 53 | Lack of EC formation | 53 |
| Foxf1 | E8.25 | Mes | 54 | Absence of vasculature in allantois | 54 |
| FoxO1 | E8.0, E11.5 | EC of umbilical vessels | 55 | Lack of chorio-allantoic fusion | 56 |
| Snai1 | E8.25 | Mes | 31 | ECs fail to form plexus | 57 |
| dHAND | E8.25 | Mes | 31 | Nd | |
| T | E7.5-E8.5 | Mes | 58 | ECs fail to form plexus, lack of chorio-allantoic fusion | 2 |
| Tbx4 | E7.5-E10.5 | Mes (not EC) | 59 | ECs fail to form plexus, lack of chorio-allantoic fusion | 31,50 |
| Cdx2/Cdx4 | E7.5 | Mes | 60 | Decreased plexus formation, lack of chorio-allantoic fusion, vessels fail to invade placenta | 60 |
| Category/gene name . | Expression in the allantois or placenta . | Ref. . | Phenotype in allantois or placenta . | Ref. . | |
|---|---|---|---|---|---|
| Age . | Area of expression . | ||||
| Vegf signaling | |||||
| Vegf | E8.5, E12.5 | Mt, labyrinthine stroma | 19,20 | Degenerating endothelium in placenta | 21 |
| Flk1 | E7.5, E8.75, E12.5 | EC, placental vasculature | 5,19,20 | Lack of mature ECs in the allantois | 22 |
| Flt1 | E8.75, E12.5 | EC, placental vasculature | 5,19,20 | Nd | |
| EC | |||||
| Pecam | E8.0 onwards | EC | 5 | None (viable) | 23 |
| VE-Cad | E8.0 onwards | EC | 5 | No allantois plexus | 24-27 |
| Hematopoietic | |||||
| Tal1 | E7.0-8.0 | EPC | 5 | Absence of blood | 28 |
| Runx1 | E8.0-8.5 | Hematopoietic precursors | 7 | Nd | |
| SMC | |||||
| SM22α | E8.25 | SMC | None (viable) | 29 | |
| αSMA | E8.25 | SMC | Nd | ||
| ECM | |||||
| Fn | E8.25 | Mes* | 30 | Nd | |
| Itgα5 | E8.25 | Mes | 31 | Nd | |
| Collagen1α (I) | E8.25 | Mes | 31 | Nd | |
| Has2 | E8.25 | Mes | 31 | Nd | |
| Vcan | E8.25 | Mes | 31 | Nd | |
| Adamts9 | E7.5 | Mes | 32 | Nd | |
| Remodeling of vascular plexus | |||||
| Nrp1 | Nd | Nd | Nd | ||
| Nrp2 | Nd | Nd | Nd | ||
| Tie1 | E8.75, E12.5 | EC, placental vasculature | 19,20 | Nd | |
| Tie2 | E8.75, E12.5 | EC, placental vasculature | 19,20 | Nd | |
| Ang1 | Nd | Nd | Lack of complexity in umbilical vessels | 33 | |
| Ang2 | Nd | Nd | Nd | ||
| Tgfβ | E7.5-8.5 | Nd | 34 | Defective chorio-allantoic fusion; lack of Flk1 expression in allantois | 35 |
| Alk1 | Nd | Nd | Nd | ||
| Alk5 | Nd | EC and SMC of placenta | 36 | Defective sprouting of allantois into placenta; lack of SMCs around allantoic vessels | 36 |
| Edd | Nd | Nd | ECs fail to form plexus, lack of chorio-allantoic fusion | 37 | |
| Lpp3 | E8.0-E10.5 | Mes | 38 | ECs fail to form plexus, lack of chorio-allantoic fusion | 38 |
| Artery versus vein | |||||
| ephrinB2 | E9.5 | Vascular plexus, UA | 39 | None | 40 |
| EphrinB4 | E9.0 | EC/UV | 39 | Nd | |
| Notch2 | E8.25 | Mes | 31,41 | Nd | |
| Dll4 | E8.25 | Arterial EC | 31 | Degenerating vasculature in placenta | 42 |
| Jag1 | E8.25 | Mes | 31 | Nd | |
| Hey1 Hey2 | E8.5, E9.0 | Mes | 43 | Vasculature in CAP but not in the labyrinth | 44 |
| Signaling molecules | |||||
| Wnt2 | E8.0-9.5 | Mes | 45 | Late gestation hemorrhage; tissue disruption in placenta | 45 |
| Wnt5a | E7.0, 8.0 | Mes | 46 | No affect on allantois | 46 |
| Wnt11 | E7.0-8.0 | Mes | 47 | Nd | |
| Rspo3 | E8.0, 8.5 | Mes | 48 | Vessels fail to invade placenta | 48,49 |
| Bmp4 | E8.25 | Mes | 50 | Small or no allantois | 51 |
| Smad1 | E7.25 | Mes | 52 | No chorio-allantoic fusion | 52 |
| Transcription factors | |||||
| Etv2 | E7.5, E8.25 | Mes | 53 | Lack of EC formation | 53 |
| Foxf1 | E8.25 | Mes | 54 | Absence of vasculature in allantois | 54 |
| FoxO1 | E8.0, E11.5 | EC of umbilical vessels | 55 | Lack of chorio-allantoic fusion | 56 |
| Snai1 | E8.25 | Mes | 31 | ECs fail to form plexus | 57 |
| dHAND | E8.25 | Mes | 31 | Nd | |
| T | E7.5-E8.5 | Mes | 58 | ECs fail to form plexus, lack of chorio-allantoic fusion | 2 |
| Tbx4 | E7.5-E10.5 | Mes (not EC) | 59 | ECs fail to form plexus, lack of chorio-allantoic fusion | 31,50 |
| Cdx2/Cdx4 | E7.5 | Mes | 60 | Decreased plexus formation, lack of chorio-allantoic fusion, vessels fail to invade placenta | 60 |
CAP indicates chorio-allantoic plate; EC, endothelial cell; ECM, extracellular matrix; EPC, endothelial precursor cells; Mt, mesothelium; Mes, mesenchyme; Nd, not defined, SMC, smooth muscle cell; UA, umbilical artery; and UV, umbilical vein.
Mes refers to expression detected by whole mount and does not rule out possible expression in ECs.