Loved ones outlierDll3 can be a structurally divergent DSL family member (Dunwoodie et al., 1997) which is expressed inside the developing brain, thymus and paraxial mesoderm; but losses in Dll3 are associated with vertebral-segmentation and rib defects in patients with spondylocostal dysostosis (Bulman et al., 2000; Turnpenny et al., 2003) as well as the pudgy mouse (Kusumi et al., 2004; Kusumi et al., 1998). Somites include vertebral precursors and are rhythmically generated in the presomitic mesoderm through coordinated interactions in between the Wnt, FGF and Notch signaling pathways (Dequeant et al., 2006). Because Dll3 is expressed inside the presomitic mesoderm, and losses in Dll3 produce defects in somite formation and patterning, it seems probably that Dll3 functions in Notch signaling throughout somitogenesis. In addition to Dll3, Dll1 can also be expressed within the presomitic mesoderm exactly where it functions in somitogenesis; on the other hand, Dll1 and Dll3 mutant mice show incredibly distinct somite defects (Dunwoodie et al., 2002; Kusumi et al., 2004; Zhang et al., 2002). Importantly, Dll3 is unable to rescue the Dll1 mutant somite phenotype in creating mouse embryos, indicating that these associated DSL ligands are not functionally equivalent (Geffers et al., 2007). Consistent with this concept, Dll1 can be a potent activating Notch ligand, even though Dll3 lacks structural qualities critical for DSL ligands to bind to Notch in trans and thereby activate Notch signaling (Geffers et al., 2007; Ladi et al., 2005). Overexpression of Dll3 in mammalian cells blocks Notch signaling and in Xenopus embyros produces phenotypes indicative of loss of Notch signaling, supporting the notion that Dll3 is a Notch antagonist (Ladi et al., 2005). Even though it’s unclear how Dll3 inhibits Notch signaling in these cellular contexts, Dll3 coexpressed with Notch is detected in the cell surface and binds Notch, suggesting a function for Dll3 in cis-inhibition. Even so, endogenous Dll3 is detected inside the Golgi and shows small if any cell surface localization (Geffers et al., 2007), suggesting that overexpression may possibly override the Dll3 Golgi retention mechanism and let Dll3 to traffic PDGF-R-alpha Proteins custom synthesis towards the cell surface. Collectively these findings suggest that Dll3 surface expression is highly regulated; on the other hand, the Golgi localization of Dll3 is difficult to