title: 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.affiliation: Divisions of Human Genetics and Orthopaedic Surgery, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. kusumi@mail.upenn.edu
authors.forename: Kenro
authors.initials: K
authors.lastname: Kusumi
authors.forename: Mizuho S
authors.initials: MS
authors.lastname: Mimoto
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Covello
authors.forename: Rosa S P
authors.initials: RS
authors.lastname: Beddington
authors.forename: Robb
authors.initials: R
authors.lastname: Krumlauf
authors.forename: Sally L
authors.initials: SL
authors.lastname: Dunwoodie
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D004413:Dysostoses / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D016695:Glycosyltransferases / Q000378:metabolism; D018257:Helix-Loop-Helix Motifs; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D019170:Somites / Q000378:metabolism* / Q000473:pathology; D013131:Spine / Q000002:abnormalities*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D016695:Glycosyltransferases; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C430525:Hes7 protein, mouse; C107407:Mesp2 protein, mouse; C064045:delta protein; C498393:LFNG protein, human; C498392:Lfng protein, mouse