Dll3 pudgy mutation differentially disrupts dynamic expression of somite genes

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. genesis 39:115–121, 2004. © 2004 Wiley‐Liss, Inc.