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Riddle DL, Blumenthal T, Meyer BJ, et al., editors. C. elegans II. 2nd edition. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press; 1997.

Cover of C. elegans II

C. elegans II. 2nd edition.

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Section IIThe Anchor Cell

The AC is the key organizer of vulval patterning and morphogenesis, and as a consequence, some mutations that affect the development of the AC also affect vulval development. Wild-type hermaphrodites have a single AC, generated after interactions between two equivalent cells (Hirsh et al. 1976; Kimble and Hirsh 1979; Kimble 1981; Seydoux and Greenwald 1989). Studies of this process, the “AC/VU decision,” have illuminated the function of lin-12 , which also mediates lateral signaling involved in specifying the fates of the VPCs.

A. The AC/VU Decision

During development of the hermaphrodite gonad, each of two cells, named Z1.ppp and Z4.aaa, has an equal chance of becoming the AC or a ventral uterine precursor cell (VU). However, in a given hermaphrodite, only one cell becomes the AC (Kimble and Hirsh 1979). Laser microsurgery experiments have shown that this outcome reflects interactions between Z1.ppp and Z4.aaa (Kimble 1981; Seydoux and Greenwald 1989). If all cells in the developing somatic gonad are ablated except for Z1.ppp and Z4.aaa, one of the two cells becomes the AC and the other becomes a VU. However, if all cells are ablated except for Z1.ppp or Z4.aaa, the remaining cell always becomes an AC. Taken together, these results suggest that Z1.ppp and Z4.aaa each makes a decision between the AC and VU fates and that signaling between them ensures that only one becomes the AC (see Fig. 3).

Figure 3. The AC/VU decision.

Figure 3

The AC/VU decision. The specification of the AC and VU fates may be viewed as having three steps prior to cell fate commitment (Seydoux and Greenwald 1989). (1) Uncommitted Z1.ppp and Z4.aaa (more...)

B. Genes Involved in the AC/VU Decision

The AC/VU decision is mediated by the activity of lin-12 and lag-2 . LIN-12 is thought to function as the receptor for LAG-2. lin-12 was implicated in the control of the AC/VU decision by the observation that null alleles cause both Z1.ppp and Z4.aaa to become ACs, whereas hypermorphic or activated alleles cause both Z1.ppp and Z4.aaa to become VUs (Greenwald et al. 1983). The predicted LIN-12 protein (Greenwald 1985; Yochem et al. 1988) is the archetype of the LIN-12/Notch protein family found in all animals (for review, see Greenwald 1994; Artavanis-Tsakonas et al. 1995). All members of this family are predicted transmembrane proteins with multiple epidermal growth factor (EGF)-like motifs and three LNR (LIN-12/Notch repeat) motifs in their extracellular domains and six cdc10/SWI6 motifs (also called ankyrin repeats) in their cytoplasmic domains. Genetic mosaic analysis suggested that lin-12 functions as the receptor for the signal between Z1.ppp and Z4.aaa (Seydoux and Greenwald 1989). Many other aspects of lin-12 expression, structure, and function have also been studied (Greenwald and Seydoux 1990; Seydoux et al. 1990; Lambie and Kimble 1991; Fitzgerald et al. 1993; Struhl et al. 1993; Sundaram and Greenwald 1993a; Chamberlin and Sternberg 1994; Wilkinson et al. 1994; Newman et al. 1995; Wilkinson and Greenwald 1995).

lag-2 was implicated in the AC/VU decision by loss-of-function alleles that lead to the production of two ACs (Lambie and Kimble 1991). Furthermore, rare gain-of-function alleles suppress the AC/VU decision defect caused by hypermorphic alleles of lin-12 (Tax et al. 1994; F. Tax et al., in prep.). lag-2 is predicted to encode a transmembrane protein with EGF-like motifs and another cysteine-based motif, the DSL domain (Henderson et al. 1994; Tax et al. 1994). These structural features are apparent in all members of a family of “DSL” proteins (for Delta, Serrate, LAG-2) thought to function as ligands for LIN-12/Notch proteins in all animals. Other aspects of lag-2 expression, structure, and function have also been studied (Lambie and Kimble 1991; Henderson et al. 1994; Tax et al. 1994; Wilkinson et al. 1994; Fitzgerald and Greenwald 1995).

C. A Feedback Mechanism during the AC/VU Decision

Genetic mosaics in which Z1.ppp and Z4.aaa differed in lin-12 activity illuminated an important aspect of the AC/VU decision (Seydoux and Greenwald 1989). Normally, the relative level of lin-12 activity in Z1.ppp and Z4.aaa is somehow assessed by the two cells before either commits to the AC or VU fates, and a feedback mechanism reinforces a stochastic initial difference between the two cells so that only one becomes an AC (Fig. 3). Analysis of lin-12 and lag-2 expression suggested that transcriptional control is a component of the inferred feedback mechanism in the AC/VU decision (Wilkinson et al. 1994). Although both lin-12 and lag-2 are initially expressed in both Z1.ppp and Z4.aaa, lin-12 expression becomes restricted to the presumptive VU and lag-2 expression becomes restricted to the presumptive AC at some point prior to commitment. This change in the expression pattern depends on lin-12 activity and appears to be functionally important for a normal AC/VU decision.

Copyright © 1997, Cold Spring Harbor Laboratory Press.
Bookshelf ID: NBK20052

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