Fig. 1. Relevant background information. (A) In the third larval stage, an inductive signal (black arrow) from the gonadal anchor cell (AC) and a lateral signal (gray arrows) from P6.p impose a 3°-3°-2°-1°-2°-3° pattern of cell fates on six equivalent VPCs, P3.p-P8.p. Cell fates can be distinguished by appropriate markers (see text and legends of Figs 5, 6). (B) Full-length LIN-12, with hallmark regions of EGF-like (EGF), LIN-12/Notch repeat (LNR), cdc10/ankyrin (ANK) repeat and PEST sequence (P). The position of the green fluorescent protein (GFP) tag is also shown. `Region 1' (r1) was shown to be sufficient to promote downregulation of membrane tethered GFP in P6.p (Shaye and Greenwald, 2002). (C) Canonical endocytic downregulation. Sub-apical adherens junctions (AJ), marked by the protein AJM-1 (Koppen et al., 2001), separate the apical surface from the basolateral surface. A receptor (white bar: extracellular domain; hatched bar: intracellular domain) marked for downregulation is internalized and trafficked to early endosomes (EE). From EEs, receptors that are tagged for downregulation are trafficked to late endosomes (LE)/multi-vesicular endosomes (MVE). An MVE-sorting step, by which the receptor is sorted into invaginating lumenal vesicles, removes the intracellular domain from the cytosol. MVE lumenal vesicles are delivered to the lysosome. (D) The first 45 amino acids of region 1 from LIN-12 and GLP-1 in C. elegans (Ce), C. briggsae (Cb) and C. remanei (Cr) (Rudel and Kimble, 2001; Rudel and Kimble, 2002) have regions of conservation. The DTS is boxed, and conserved residues analyzed in this study are marked by asterisks. The conserved CSL-binding region (Kovall and Hendrickson, 2004) is also indicated. Alignments were obtained with the ClustalW feature of MacVector (Accelrys).