International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


THE PUDGY/SPONDYLOCOSTAL DYSOSTOSIS GENE DELTA-LIKE 3 IS REQUIRED FOR CYCLING IN SOMITOGENESIS & IS DYNAMICALLY EXPRESSED IN NEURAL DEVELOPMENT

Kenro Kusumi
U.Penn/Children's Hospital of Philadelphia
ARC-1002C
3615 Civic Center Blvd
Philadelphia PA 19104, USA

Co-Authors: 1)Dunwoodie, S., 2)Krumlauf, R.
Institutions: 1)The Victor Chang Cardiac Research Institute, 2)The Stowers Institute for Biomedical Research

Genes in the Notch signaling pathway play key roles in embryonic patterning. We have previously shown that the pudgy (Dll3pu) mouse and human spondylocostal dysostosis (SD, MIM277300) are mutations in the Notch ligand, Delta-like 3. Both Dll3pu and SD display extensive vertebral and rib malformations, resulting from defective segmentation of the paraxial mesoderm. The Notch modulator, lunatic fringe (Lfng), is dynamically expressed in the presomitic mesoderm during each somite cycle. In Dll3pu mutants, altered Lfng cycling is detected at 8.5 dpc, and completely disrupted at 9.5 dpc., This suggests that Dll3 is required for maintenance of Lfng cycling, and that defects in the somite clock underlie spondylocostal dysostosis.

Dll3 is also expressed throughout neural patterning. In particular, we have identified dynamic expression of Dll3 between 9.0 and 11.5 dpc in hindbrain development. Interestingly, SD patients exhibit facial torticollis, a defect potentially related to neural development, but do not show overt signs of mental retardation or gross neurological impairment. Dll3 and Notch pathway genes are expressed in laminar domains during neural development, and in Dll3pu mutants, we have characterized ependymal laminar defects. Examination of SD patients and analysis of Dll3pu mice are ongoing, to define Dll3 function in neural patterning.


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