Table 2.
Genes of the planar cell polarity pathway—involvement in mouse NTDs
| Gene | Mutant/genotype | Protein | NTD phenotype | References |
|---|---|---|---|---|
| Single gene effects | ||||
| Vangl2 | Loop-tail (Lp, Lpm1Jus); Lp/Lp | Transmembrane protein | Craniorachischisis. Occasional spina bifida in Lp/+ | (91,92,156,157) |
| Scrb1 | Circle-tail; Crc/Crc | Cytoplasmic polarity protein | Craniorachischisis | (93) |
| Celsr1 | Crash; Crsh/Crsh | Seven-pass transmembrane protein | Craniorachischisis | (158) |
| Spin-cycle; Scy/Scy | Craniorachischisis | |||
| Ptk7 (CCK-4) | Ptk7mu/mu (truncating gene-trap allele) | Transmembrane receptor tyrosine kinase-like protein | Craniorachischisis | (94) |
| Paralogous gene interactions | ||||
| Dv11/2 | Dvl1−/−; Dvl2−/− | Cytoplasmic signalling proteins | Craniorachischisis | (159) |
| Dvl2/3 | Dv12−/−; Dvl3+/− (Dv12−/−; 3−/− die before E8.5) | Craniorachischisis | (101) | |
| Fz3/6 | Fz3−/−; Fz6−/− | Transmembrane receptor protein | Craniorachischisis | (160) |
| Smurf1/2 | Smurf1−/−; Smurf2−/− | Ubiquitin ligase | No closure at E8.5 | (61) |
| Smurf1−/−; 2+/− or 1+/−;2−/− | Spina bifida and/or exencephaly | |||
| Interactions between different genes | ||||
| Vangl2/Scrb1 | Lp/+; Crc/+ | See above | Craniorachischisis | (102) |
| Vangl2/Dvl3 | Lp/+;Dvl3−/− | See above | Craniorachischisis | (101) |
| Lp/+;Dvl3+/− | Craniorachishisis or exencephaly | |||
| Vangl2/Vangl1 | Lp/+; Vang1gt/+ | Transmembrane protein | Craniorachischisis | (98) |
| Vangl2/Ptk7 | Lp/+; Ptk7+/mu | See above | Spina bifida | (94) |
| Vangl2/Wnt5a | Lp/+; Wnt5a−/− | Secreted signalling protein | Craniorachischisis | (161) |
| Vangl2/Sfrp1,2,5 | Lp/+; Sfrp1−/−; Sfrp2−/−; Sfrp5+/− | Secreted Wnt antagonist | Craniorachischsis | (162) |
| Lp/+; Sfrp1−/−; Sfrp2+/−; Sfrp5−/− | Spina bifida | |||
| Vangl2/Cthrc1 | Lp/+; Cthrc1LacZ/LacZ | Secreted glycoprotein, Wnt co-factor | Exencephaly | (100) |
| Vangl2/Grhl3 | Lp/+; Grhl3ct/ct | Transcription factor | Severe spina bifida | (163) |
| Vangl2/cobl | Lp/+; coblC101/C101 | Actin nucleator | Exencephaly | (99) |