This article was accepted for inclusion in Developmental Dynamics 236 #6—Special Focus on Segmentation.
Special Issue Disease Connections
Dll3 and Notch1 genetic interactions model axial segmental and craniofacial malformations of human birth defects†
Version of Record online: 11 SEP 2007
Copyright © 2007 Wiley-Liss, Inc.
Volume 236, Issue 10, pages 2943–2951, October 2007
How to Cite
Loomes, K. M., Stevens, S. A., O'Brien, M. L., Gonzalez, D. M., Ryan, M. J., Segalov, M., Dormans, N. J., Mimoto, M. S., Gibson, J. D., Sewell, W., Schaffer, A. A., Nah, H.-D., Rappaport, E. F., Pratt, S. C., Dunwoodie, S. L. and Kusumi, K. (2007), Dll3 and Notch1 genetic interactions model axial segmental and craniofacial malformations of human birth defects. Dev. Dyn., 236: 2943–2951. doi: 10.1002/dvdy.21296
- Issue online: 18 SEP 2007
- Version of Record online: 11 SEP 2007
- Manuscript Accepted: 6 JUL 2007
- Burroughs Wellcome Fund Hitchings-Elion Fellowship
- NIH RO1. Grant Number: AR050687
- NHMRC. Grant Number: 404804
- Pfizer Foundation Australia Senior Research Fellowship
- hard palate;
- notch pathway;
Mutations in the Notch1 receptor and delta-like 3 (Dll3) ligand cause global disruptions in axial segmental patterning. Genetic interactions between members of the notch pathway have previously been shown to cause patterning defects not observed in single gene disruptions. We examined Dll3-Notch1 compound mouse mutants to screen for potential gene interactions. While mice heterozygous at either locus appeared normal, 30% of Dll3-Notch1 double heterozygous animals exhibited localized, segmental anomalies similar to human congenital vertebral defects. Unexpectedly, double heterozygous mice also displayed statistically significant reduction of mandibular height and elongation of maxillary hard palate. Examination of somite-stage embryos and perinatal anatomy and histology did not reveal any organ defects, so we used microarray-based analysis of Dll3 and Notch1 mutant embryos to identify gene targets that may be involved in notch-regulated segmental or craniofacial development. Thus, Dll3-Notch1 double heterozygous mice model human congenital scoliosis and craniofacial disorders. Developmental Dynamics 236:2943–2951, 2007. © 2007 Wiley-Liss, Inc.