Mutations in the genes
lin-12 and
lin-17 cause cells that normally differ instead to appear identical. In general,
lin-12 mutations cause certain non-identical homologues (generated as lineally equivalent descendants from morphologically similar progenitors that undergo identical division patterns) to adopt the same fate [Greenwald et al., Cell 34, 435 (1983)], whereas
lin-17 mutations appear to cause certain non-identical sisters to adopt the same fate (see below). lin- 12 and
lin-17 mutations affect partially overlapping sets of cell lineages (including Z1, Z4, Pn.p, B and M) at different stages of development and are expressed independently in doubly mutant strains. Defects in the male B, Z1 and Z4 lineages in
lin-17 mutants precede those in
lin-12 mutants, while defects in the hermaphrodite P(3-8).p lineages in
lin-12 mutants precede those in
lin-17 mutants. Thus, lin- 12 and
lin-17 may normally function sequentially within each of several different lineages to specify certain cell fates. The phenotypes resulting from, and interactions between, mutations in
lin-12 and
lin-17 are exemplified by the hermaphrodite and male Z1 and Z4 lineages. In wild-type hermaphrodites, Z1 and Z4 each produce a ventral uterine precursor cell (VU) and a cell (ac/VU) that becomes either a VU or an anchor cell (ac)(see Fig. 1). Similarly, in wild- type males, Z1 and Z4 each produce a vas deferens precursor cell (VD) and a cell (lc/VD) that becomes either a linker cell (lc) or a VD cell (see Fig. 2). In a given animal only one of the ac/VU's or lc/VD's become an ac or lc, respectively. In hermaphrodites carrying a null allele of
lin-12 ['
lin-12(0)'], the VU cells are sometimes transformed into ac's. (This transformation occurs in addition to that of both ac/VU's becoming ac's, which we have described previously [ibid.].) Thus,
lin-12(0) hermaphrodites have up to four ac's, suggesting that normally there is a low level of
lin-12 activity in ac's. In semidominant
lin-12 mutants ['
lin-12(d)'], all four cells are VU 's, suggesting that during wild-type development there is a high level of
lin-12 activity in the VU's. This high level of
lin-12 activity may be set intrinsically in Z1.ppa and Z4.aap (which normally are both VU's) and by cell-cell interactions in the ac/VU that becomes a VU. Thus, an intrinsically-set high level of
lin-12 activity may exclude the VU cells from the ventral uterine 'equivalence group' (comprising those cells that can become ac's in the wild type). In males, the lc/VD's and VD's are similarly affected by
lin-12(d) and
lin-12(0) mutations:
lin-12(d) males can have four VD's and
lin-12(0) males can have four lc's. The persistence of some VU's or VD's in the two lin- 12(0) strains examined suggests either that these strains have residual
lin-12 activity or that
lin-12 is not absolutely required for the production of these cell types. The transformations in cell fates caused by
lin-17 mutants can be exemplified by the male Z1 and Z4 lineages. In wild-type males, during the L1-L2 divisions, Z1 and Z4 each produce one daughter that becomes a distal tip cell (dtc) and another daughter that generates four cells, including a VD and an lc/VD (Fig. 2). In
lin-17 males Z1 and Z4 each can generate eight progeny during the L1-L2 divisions.
lin-17 males often have two lc's and no dtc's. In addition, the germ line nuclei undergo meiosis prematurely, consistent with Judith Kimble's dtc-ablation experiments [Develop. Biol. 81, 208], which demonstrated that the dtc is necessary for continued mitosis of germ nuclei. If
lin-17 causes both daughters of Z1 and Z4 to be identical, then
lin-17 males should have four lc/VD's instead of two as in wild- type. However, only one (or two) of the lc/VD's would become a lc if the cell-cell interactions responsible for allowing only a single lc in the wild type are still functioning in
lin-17 males. To test for the presence of multiple lc/VD's, we used a
lin-12(0) mutation, which transforms lc/VD's (as well as VD's) into lc's. While
lin-17 males have one or two lc's and
lin-12(0) males have from two to four lc's, males carrying both mutations have from two to seven lc's. These results establish that there are indeed additional lc/VD's in
lin-17 males, which indicates that the fates of both Z1 and both Z4 daughters are identical and reveals that the
lin-17 and
lin-12(0) mutations are expressed independently.