Cell-Cycle Regulation of NOTCH Signaling during C. elegans Vulval Development

  • Stefanie Nusser-Stein ,
  • Anjie Beyer ,
  • Ivo Rimann ,
  • Magdalene Adamczyk ,
  • Nir Piterman ,
  • Alex Hajnal ,
  • Jasmin Fisher

Molecular Systems Biology, Featured Article 8:618 |

During metazoan development, NOTCH signaling is involved in a multitude of cell fate decisions, especially when single cells are selected from a group of equivalent precursor cells (Fanto and Mlodzik, 1999; Baron et al, 2002). Well-studied examples include Drosophila wing formation, mammalian angiogenesis (Liu et al, 2003), or neuronal fate decisions (Hitoshi et al, 2002; Aguirre et al, 2010). Moreover, the NOTCH pathway is deregulated in different types of human cancer (Stylianou et al, 2006; Sharma et al, 2007). The binding of a DSL (Delta/Serrate/LAG-2) family NOTCH ligand activates two specific proteolytic cleavage events that result in the release of the NOTCH intracellular domain (NICD) from the plasma membrane (Baron, 2003). NICD then enters the nucleus, where it interacts with CSL (CBF1, Suppressor of Hairless, LAG-1) family transcription factors to induce the expression of target genes. Therefore, NOTCH signaling is often used as a cell fate switch that can be rapidly turned on.