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Gene Review

Dll3  -  delta-like 3 (Drosophila)

Mus musculus

Synonyms: Delta-like protein 3, Delta3, Drosophila Delta homolog 3, M-Delta-3, pu, ...
 
 
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Disease relevance of Dll3

  • Dynamic expression patterns of the pudgy/spondylocostal dysostosis gene Dll3 in the developing nervous system [1].
 

High impact information on Dll3

  • Dll3 is mutated in the X-ray-induced mouse mutant pudgy (pu), causing a variety of vertebrocostal defects similar to SD phenotypes [2].
  • The mouse pudgy mutation disrupts Delta homologue Dll3 and initiation of early somite boundaries [3].
  • Histological and molecular marker analyses show that the pu mutation disrupts the proper formation of morphological borders in early somite formation and of rostral-caudal compartment boundaries within somites [3].
  • Additionally, our epistatic analysis revealed that Mesp2 affects rostrocaudal properties more directly than Dll1 or Dll3 [4].
  • 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 [5].
 

Biological context of Dll3

 

Anatomical context of Dll3

  • The three major sites of expression implicate Dll3 in somitogenesis and neurogenesis and in the production of tissue from the primitive streak and tailbud [8].
  • 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 [5].
  • Temporal analysis of Dll3 expression from 9.0 to 11.0 dpc reveals that it is strongly expressed in laminar columns linked with regions of neuronal differentiation and hindbrain segmentation [1].
 

Other interactions of Dll3

  • The Notch ligand genes Dll1 and Dll3 were reduced or altered in expression in a significant proportion of mutants [9].
  • Lfng-deficient mice and Dll3-deficient mice exhibit very similar defects, and marker analysis suggests that progression of the segmentation clock is disrupted in Dll3 mutants [10].
  • Rather, vertebral column and sclerotomal phenotypes are reminiscent of the phenotypes observed in the segmentation/somitogenesis mutants rachiterata and pudgy [11].
  • We show that Notch1, 2, Jag1-2, Dll-3, Rbpsuh and Dtx2 transcripts are expressed at all stages [12].
  • At present, the precise function of Pw1 is not understood; however, we note that Pw1 maps to the proximal region of chromosome 7 near the axial segmentation mutant pudgy which shows severe perturbation of axial skeletal and muscle structures [13].
 

Analytical, diagnostic and therapeutic context of Dll3

  • 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 [5].
  • Microdissection and microcloning from the proximal region of mouse chromosome 7: isolation of clones genetically linked to the pudgy locus [7].

References

  1. Dynamic expression patterns of the pudgy/spondylocostal dysostosis gene Dll3 in the developing nervous system. Kusumi, K., Dunwoodie, S.L., Krumlauf, R. Mech. Dev. (2001) [Pubmed]
  2. Mutations in the human delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis. Bulman, M.P., Kusumi, K., Frayling, T.M., McKeown, C., Garrett, C., Lander, E.S., Krumlauf, R., Hattersley, A.T., Ellard, S., Turnpenny, P.D. Nat. Genet. (2000) [Pubmed]
  3. The mouse pudgy mutation disrupts Delta homologue Dll3 and initiation of early somite boundaries. Kusumi, K., Sun, E.S., Kerrebrock, A.W., Bronson, R.T., Chi, D.C., Bulotsky, M.S., Spencer, J.B., Birren, B.W., Frankel, W.N., Lander, E.S. Nat. Genet. (1998) [Pubmed]
  4. Feedback loops comprising Dll1, Dll3 and Mesp2, and differential involvement of Psen1 are essential for rostrocaudal patterning of somites. Takahashi, Y., Inoue, T., Gossler, A., Saga, Y. Development (2003) [Pubmed]
  5. 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. Dunwoodie, S.L., Clements, M., Sparrow, D.B., Sa, X., Conlon, R.A., Beddington, R.S. Development (2002) [Pubmed]
  6. New mutant mouse with skeletal deformities caused by mutation in delta like 3 (Dll3) gene. Shinkai, Y., Tsuji, T., Kawamoto, Y., Kunieda, T. Exp. Anim. (2004) [Pubmed]
  7. Microdissection and microcloning from the proximal region of mouse chromosome 7: isolation of clones genetically linked to the pudgy locus. Greenfield, A.J., Brown, S.D. Genomics (1987) [Pubmed]
  8. Mouse Dll3: a novel divergent Delta gene which may complement the function of other Delta homologues during early pattern formation in the mouse embryo. Dunwoodie, S.L., Henrique, D., Harrison, S.M., Beddington, R.S. Development (1997) [Pubmed]
  9. Expression of Notch signaling pathway genes in mouse embryos lacking beta4galactosyltransferase-1. Chen, J., Lu, L., Shi, S., Stanley, P. Gene Expr. Patterns (2006) [Pubmed]
  10. Segmentation defects of Notch pathway mutants and absence of a synergistic phenotype in lunatic fringe/radical fringe double mutant mice. Zhang, N., Norton, C.R., Gridley, T. Genesis (2002) [Pubmed]
  11. Early mesodermal phenotypes in splotch suggest a role for Pax3 in the formation of epithelial somites. Schubert, F.R., Tremblay, P., Mansouri, A., Faisst, A.M., Kammandel, B., Lumsden, A., Gruss, P., Dietrich, S. Dev. Dyn. (2001) [Pubmed]
  12. Developmental expression of the Notch signaling pathway genes during mouse preimplantation development. Cormier, S., Vandormael-Pournin, S., Babinet, C., Cohen-Tannoudji, M. Gene Expr. Patterns (2004) [Pubmed]
  13. Pw1, a novel zinc finger gene implicated in the myogenic and neuronal lineages. Relaix, F., Weng, X., Marazzi, G., Yang, E., Copeland, N., Jenkins, N., Spence, S.E., Sassoon, D. Dev. Biol. (1996) [Pubmed]
 
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