Worm Breeder's Gazette 8(1): 12

These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

lin-12 and lin-17 Act Sequentially to Specify Cell Fates in Certain Cell Lineages

P. Sternberg, B. Horvitz

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.