Dll3 pudgy mutation differentially disrupts dynamic expression of somite genes.

Abstract

Mutations in the notch ligand delta-like 3 have been identified in both the pudgy mouse (Dll3(pu); Kusumi et al.: Nat Genet 19:274-278, 1998) and the human disorder spondylocostal dysostosis (SCD; Bulman et al.: Nat Genet 24:438-441, 2000), and a targeted mutation has been generated (Dll3(neo); Dunwoodie et al.: Development 129:1795-1806, 2002). Vertebral and rib malformations deriving from defects in somitic patterning are key features of these disorders. In the mouse, notch pathway genes such as Lfng, Hes1, Hes7, and Hey2 display dynamic patterns of expression in paraxial mesoderm, cycling in synchrony with somite formation (Aulehla and Johnson: Dev Biol 207:49-61, 1999; Forsberg et al.: Curr Biol 8:1027-1030, 1998; Jouve et al.: Development 127:1421-1429, 2000; McGrew et al.: Curr Biol 8:979-982, 1998; Nakagawa et al.: Dev Biol 216:72-84, 1999). We report here that the Dll3(pu) mutation has different effects on the expression of cycling (Lfng and Hes7) and stage-specific genes (Hey3 and Mesp2). This suggests a more complex situation than a single oscillatory mechanism in somitogenesis and provides an explanation for the unique radiological features of the human DLL3-type of SCD.

• Authors: Kenro Kusumi, Mizuho S Mimoto, Kelly L Covello, Rosa S P Beddington, Robb Krumlauf, Sally L Dunwoodie
• Journal: Genesis (New York, N.Y. : 2000) (Genesis) Vol. 39 Issue 2 Pg. 115-21 (Jun 2004) ISSN: 1526-954X [Print] United States
• PMID: 15170697 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2004 Wiley-Liss, Inc.

Chemical References

• Basic Helix-Loop-Helix Transcription Factors
• Hes7 protein, mouse
• Homeodomain Proteins
• Intracellular Signaling Peptides and Proteins
• Membrane Proteins
• Mesp2 protein, mouse
• Repressor Proteins
• Transcription Factors
• delta protein
• Glycosyltransferases
• LFNG protein, human
• Lfng protein, mouse

Topics

• Animals
• Basic Helix-Loop-Helix Transcription Factors
• Dysostoses (embryology)
• Gene Expression Regulation, Developmental
• Glycosyltransferases (metabolism)
• Helix-Loop-Helix Motifs
• Homeodomain Proteins (genetics, metabolism)
• Intracellular Signaling Peptides and Proteins
• Membrane Proteins (genetics, metabolism)
• Mesoderm (cytology, pathology)
• Mice
• Mice, Knockout
• Mutation
• Repressor Proteins (metabolism)
• Signal Transduction
• Somites (metabolism, pathology)
• Spine (abnormalities)
• Transcription Factors (metabolism)