Axial skeletal defects caused by mutation in the spondylocostal dysplasia/pudgy geneDll3are associated with disruption of the segmentation clock within the presomitic mesoderm
| Autor: | Xin Sa, Rosa S. P. Beddington, Melanie Clements, Duncan B. Sparrow, Sally L. Dunwoodie, Ronald A. Conlon |
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| Rok vydání: | 2002 |
| Předmět: |
Naphthols
Biology Osteochondrodysplasias LFNG Mice medicine Paraxial mesoderm Animals Humans Molecular Biology HEY1 Alleles In Situ Hybridization Mice Knockout Receptors Notch Triazines Intracellular Signaling Peptides and Proteins Gene Expression Regulation Developmental Membrane Proteins Gene targeting medicine.disease Null allele Mice Mutant Strains Spondylocostal dysostosis Cell biology Somite medicine.anatomical_structure Somites Dysplasia Gene Targeting Mutation Cancer research Signal Transduction Developmental Biology |
| Zdroj: | Development. 129:1795-1806 |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.129.7.1795 |
| Popis: | A loss-of-function mutation in the mouse delta-like3 (Dll3) gene has been generated following gene targeting, and results in severe axial skeletal defects. These defects, which consist of highly disorganised vertebrae and costal defects, are similar to those associated with the Dll3-dependent pudgy mutant in mouse and with spondylocostal dysplasia (MIM 277300) in humans. This study demonstrates that Dll3neo and Dll3pu are functionally equivalent alleles with respect to the skeletal dysplasia, and we suggest that the three human DLL3 mutations associated with spondylocostal dysplasia are also functionally equivalent to the Dll3neo null allele. Our phenotypic analysis of Dll3neo/Dll3neo mutants shows that the developmental origins of the skeletal defects lie in delayed and irregular somite formation, which results in the perturbation of anteroposterior somite polarity. As the expression of Lfng, Hes1, Hes5 and Hey1 is disrupted in the presomitic mesoderm, we suggest that the somitic aberrations are founded in the disruption of the segmentation clock that intrinsically oscillates within presomitic mesoderm. |
| Databáze: | OpenAIRE |
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