Health Topics
Official websites use .gov
A
.gov website belongs to an official government
organization in the United States.
Secure .gov websites use HTTPS
A
lock (
) or https:// means you’ve safely connected to
the .gov website. Share sensitive information only on official,
secure websites.
Normal Function
The DLL3 gene provides instructions for making a protein that helps control (regulate) the Notch pathway, an important pathway in embryonic development. The Notch pathway plays a critical role in the development of vertebrae. Specifically, the DLL3 protein and the Notch pathway are involved in separating future vertebrae from one another during early development, in a complex process called somite segmentation. Although the exact mechanism of somite segmentation is unclear, it appears to require the activity of several proteins in the Notch pathway, including the NOTCH1 protein, to be turned on and off (oscillate) in a specific pattern.
The DLL3 protein regulates the activity of the NOTCH1 protein. The DLL3 protein attaches (binds) to the inactive NOTCH1 protein and isolates (sequesters) it or marks it to be broken down so that it cannot be activated.
Health Conditions Related to Genetic Changes
Spondylocostal dysostosis
At least 20 mutations in the DLL3 gene have been found to cause spondylocostal dysostosis type 1, the most common type of spondylocostal dysostosis. This condition is characterized by the abnormal development of bones in the spine and ribs. The known mutations in the DLL3 gene prevent the production of any protein or lead to the production of an abnormally short, nonfunctional protein. When the DLL3 protein is nonfunctional or absent, the NOTCH1 protein is abnormally active and does not oscillate, so somite segmentation does not occur properly. This results in the malformation and fusion of the bones of the spine and ribs seen in spondylocostal dysostosis type 1.
More About This Health ConditionOther Names for This Gene
- delta-like 3 (Drosophila)
- delta-like protein 3
- delta-like protein 3 isoform 1 precursor
- delta-like protein 3 isoform 2 precursor
- delta3
- DLL3_HUMAN
- drosophila Delta homolog 3
- SCDO1
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Bulman MP, Kusumi K, Frayling TM, McKeown C, Garrett C, Lander ES, Krumlauf R, Hattersley AT, Ellard S, Turnpenny PD. Mutations in the human delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis. Nat Genet. 2000 Apr;24(4):438-41. doi: 10.1038/74307. Citation on PubMed
- Chapman G, Sparrow DB, Kremmer E, Dunwoodie SL. Notch inhibition by the ligand DELTA-LIKE 3 defines the mechanism of abnormal vertebral segmentation in spondylocostal dysostosis. Hum Mol Genet. 2011 Mar 1;20(5):905-16. doi: 10.1093/hmg/ddq529. Epub 2010 Dec 7. Citation on PubMed
- Dunwoodie SL, Clements M, Sparrow DB, Sa X, Conlon RA, Beddington RS. Axial skeletal defects caused by mutation in the spondylocostal dysplasia/pudgy gene Dll3 are associated with disruption of the segmentation clock within the presomitic mesoderm. Development. 2002 Apr;129(7):1795-806. doi: 10.1242/dev.129.7.1795. Citation on PubMed
- Ferjentsik Z, Hayashi S, Dale JK, Bessho Y, Herreman A, De Strooper B, del Monte G, de la Pompa JL, Maroto M. Notch is a critical component of the mouse somitogenesis oscillator and is essential for the formation of the somites. PLoS Genet. 2009 Sep;5(9):e1000662. doi: 10.1371/journal.pgen.1000662. Epub 2009 Sep 25. Citation on PubMed or Free article on PubMed Central
- Gibb S, Maroto M, Dale JK. The segmentation clock mechanism moves up a notch. Trends Cell Biol. 2010 Oct;20(10):593-600. doi: 10.1016/j.tcb.2010.07.001. Epub 2010 Aug 18. Citation on PubMed or Free article on PubMed Central
- Ladi E, Nichols JT, Ge W, Miyamoto A, Yao C, Yang LT, Boulter J, Sun YE, Kintner C, Weinmaster G. The divergent DSL ligand Dll3 does not activate Notch signaling but cell autonomously attenuates signaling induced by other DSL ligands. J Cell Biol. 2005 Sep 12;170(6):983-92. doi: 10.1083/jcb.200503113. Epub 2005 Sep 6. Citation on PubMed or Free article on PubMed Central
- Oginuma M, Takahashi Y, Kitajima S, Kiso M, Kanno J, Kimura A, Saga Y. The oscillation of Notch activation, but not its boundary, is required for somite border formation and rostral-caudal patterning within a somite. Development. 2010 May;137(9):1515-22. doi: 10.1242/dev.044545. Epub 2010 Mar 24. Citation on PubMed
- Serth K, Schuster-Gossler K, Kremmer E, Hansen B, Marohn-Kohn B, Gossler A. O-fucosylation of DLL3 is required for its function during somitogenesis. PLoS One. 2015 Apr 9;10(4):e0123776. doi: 10.1371/journal.pone.0123776. eCollection 2015. Citation on PubMed or Free article on PubMed Central
- Sparrow DB, Chapman G, Turnpenny PD, Dunwoodie SL. Disruption of the somitic molecular clock causes abnormal vertebral segmentation. Birth Defects Res C Embryo Today. 2007 Jun;81(2):93-110. doi: 10.1002/bdrc.20093. Citation on PubMed
- Turnpenny PD, Sloman M, Dunwoodie S. Spondylocostal Dysostosis, Autosomal Recessive. 2009 Aug 25 [updated 2023 Aug 17]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK8828/ Citation on PubMed
- Turnpenny PD, Whittock N, Duncan J, Dunwoodie S, Kusumi K, Ellard S. Novel mutations in DLL3, a somitogenesis gene encoding a ligand for the Notch signalling pathway, cause a consistent pattern of abnormal vertebral segmentation in spondylocostal dysostosis. J Med Genet. 2003 May;40(5):333-9. doi: 10.1136/jmg.40.5.333. Citation on PubMed or Free article on PubMed Central
The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.