Gene function identified using allantois culture as a model system
| Category/gene name . | Type of molecule . | LOF/GOF (method) . | Effect on allantois culture . | Inferred function . | Ref. . |
|---|---|---|---|---|---|
| VE-Cad function and signaling | |||||
| VE-Cad | Cell-cell adhesion | LOF (null mutant and Ab) | Disconnected ECs in plexus; loss of nuclear pSmad2/3 levels; expression of Survivin in all ECs | EC motility; addition of ECs to new sprouts; plexus stabilization; regulation of TGFβ signaling; restriction of Survivin expression to tip ECs | 24,25,127,128 |
| VE-PTP | Phosphatase | LOF (null mutant and Ab) | Excess EC coverage and simple monolayer architecture of ECs | Decreased EC proliferation | 116,117 |
| Gas1 | Cell cycle | LOF (null mutant) | Apoptosis of mesenchymal cells | EC survival | 125 |
| Lipid function | |||||
| Sphingosine-1-phosphate | Lipid | GOF (added to culture) | Promotes plexus formation in serum-deprived cultures | Promotes vasculogenesis and vascular outgrowth | 119 |
| Autotaxin | Lipid synthesis | GOF (added to culture) | Prevents plexus disintegration in serum-deprived conditions | Plexus stabilization | 121 |
| Lysophosphatidic acid | Lipid | GOF (added to culture) | Prevents plexus disintegration in serum deprived conditions | Plexus stabilization | 121 |
| PI3K signaling | |||||
| PI3K | Kinase | LOF (inhibitor) | Decrease in sprout formation | Angiogenesis | 126 |
| Arap3 | GTPase | LOF (null mutant) | Decrease in sprout formation | Angiogenesis | 126 |
| RA-GEF1 | GTPase | LOF (null mutant) | Failure to form vascular plexus | Controls activation of RAP1; controls induction of VE-Cad; promotes plexus formation | 122 |
| Pdgfb | Growth factor | GOF (GF in culture) | Promotes plexus formation in low serum conditions | EC survival or maintenance | 123 |
| Hdac | Deacetylase | LOF (inhibitor) | Decrease in vascular network formation | Increased commitment of progenitors to ECs | 124 |
| Bmp9 | Signaling | GOF (GF in culture) | Promotes formation of a disorganized plexus | Increased EC proliferation | 129 |
| Bmp4 | Signaling | LOF (inhibitor) | Decrease in plexus formation | Recruitment of mural cells that promote plexus stability | 54 |
| Category/gene name . | Type of molecule . | LOF/GOF (method) . | Effect on allantois culture . | Inferred function . | Ref. . |
|---|---|---|---|---|---|
| VE-Cad function and signaling | |||||
| VE-Cad | Cell-cell adhesion | LOF (null mutant and Ab) | Disconnected ECs in plexus; loss of nuclear pSmad2/3 levels; expression of Survivin in all ECs | EC motility; addition of ECs to new sprouts; plexus stabilization; regulation of TGFβ signaling; restriction of Survivin expression to tip ECs | 24,25,127,128 |
| VE-PTP | Phosphatase | LOF (null mutant and Ab) | Excess EC coverage and simple monolayer architecture of ECs | Decreased EC proliferation | 116,117 |
| Gas1 | Cell cycle | LOF (null mutant) | Apoptosis of mesenchymal cells | EC survival | 125 |
| Lipid function | |||||
| Sphingosine-1-phosphate | Lipid | GOF (added to culture) | Promotes plexus formation in serum-deprived cultures | Promotes vasculogenesis and vascular outgrowth | 119 |
| Autotaxin | Lipid synthesis | GOF (added to culture) | Prevents plexus disintegration in serum-deprived conditions | Plexus stabilization | 121 |
| Lysophosphatidic acid | Lipid | GOF (added to culture) | Prevents plexus disintegration in serum deprived conditions | Plexus stabilization | 121 |
| PI3K signaling | |||||
| PI3K | Kinase | LOF (inhibitor) | Decrease in sprout formation | Angiogenesis | 126 |
| Arap3 | GTPase | LOF (null mutant) | Decrease in sprout formation | Angiogenesis | 126 |
| RA-GEF1 | GTPase | LOF (null mutant) | Failure to form vascular plexus | Controls activation of RAP1; controls induction of VE-Cad; promotes plexus formation | 122 |
| Pdgfb | Growth factor | GOF (GF in culture) | Promotes plexus formation in low serum conditions | EC survival or maintenance | 123 |
| Hdac | Deacetylase | LOF (inhibitor) | Decrease in vascular network formation | Increased commitment of progenitors to ECs | 124 |
| Bmp9 | Signaling | GOF (GF in culture) | Promotes formation of a disorganized plexus | Increased EC proliferation | 129 |
| Bmp4 | Signaling | LOF (inhibitor) | Decrease in plexus formation | Recruitment of mural cells that promote plexus stability | 54 |
Ab indicates antibody; LOF, loss of function; GOF, gain of function; and GF, growth factor.