LIN-12/Notch signaling: lessons from worms and flies (original) (raw)

  1. Iva Greenwald1
  2. Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University College of Physicians and Surgeons, New York, New York 10032 USA

LIN-12/Notch proteins function as receptors for intercellular signals during development. Many aspects of LIN-12/Notch-mediated signaling have been elucidated through studies of cell–cell interactions that occur during_Caenorhabditis elegans_ and _Drosophila melanogaster_development. The basic principles that operate in these lower organisms have also been shown to apply to vertebrates (for review, see Gridley 1997). Molecular features defined in lower organisms have also been shown to be conserved in vertebrates, including components of the signaling and signal transduction systems (for review, see Weinmaster 1997). The focus of this paper is on what has been learned about LIN-12/Notch signaling from invertebrates. First, a description of roles for LIN-12/Notch proteins in development is given, using different model cell fate decisions to illustrate various features. A discussion of the mechanism of LIN-12/Notch signal transduction follows, including new in vivo evidence that favors the direct participation of the intracellular domain of LIN-12/Notch proteins in regulating target gene expression. Finally, other influences on LIN-12/Notch activity are discussed, particularly protein turnover and protein processing.

The LIN-12/Notch “pathway”

Genetic studies have identified many conserved components that are important for LIN-12/Notch signaling. Table1 summarizes the C. elegans and_Drosophila_ genes involved in LIN-12/Notch signaling mentioned here, and their vertebrate counterparts. Of particular note is that transmembrane protein ligands of the conserved Delta/Serrate/LAG-2 (DSL) family activate LIN-12/Notch signal transduction (for review, seeWeinmaster 1997) and that many LIN-12/Notch outputs are mediated by a transcription factor named Suppressor of Hairless [Su(H)] in Drosophila and LAG-1 in C. elegans (seeSchweisguth and Posakony 1994; Bailey and Posakony 1995; LeCourtois and Schweisguth 1995; Christensen et al. 1996). One “pathway” involving Su(H) is considered below and is diagrammed in Figure 2(below). However, there is evidence that certain responses to activated Notch do not depend on Su(H) (Lecourtois and Schweisguth 1995; Shawber …