Worm Breeder's Gazette 11(4): 101

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More on lin-44

Michael Herman and Bob Horvitz

Figure 1

During C.  elegans development the two sister cells generated by 
most cell divisions differ in their fates.  Mutations that cause such 
normally asymmetric cell divisions either to become symmetric or to 
reverse the polarity of their asymmetry may identify genes responsible 
for the control of asymmetric cell divisions lin-44.Last year we 
reported the isolation of a mutation defining a new gene that affects 
certain asymmetric cell divisions (Herman and Horvitz, CSH C.  elegans 
Meeting Abstracts 1989, p.  277.) The mutation lin-44(n1792) primarily 
causes certain asymmetric cell divisions to be reversed in polarity.  
The B, U, F and T cell lineages are all affected in males, resulting 
in defective male tails.  The T lineage is also affected in 
hermaphrodites, causing the phasmids (sensory structures in the tail) 
in both sexes to fail to fill with fluorescent dyes.  In addition, 
some hermaphrodites are egg-laying defective.
Using a non-complementation screen, we have obtained another lin-44 
allele, n2111.  The n2111 allele behaves similarly to n1792 when 
homozygous and when heterozygous with the wild-type allele or with a 
deficiency.  Also, both homozygotes look similar to n1792/Df and 
n2111/Df heterozygotes and to the n1792/n2111 heterozygote.  Thus both 
n1792 and n2111 appear to be reduction-of-function alleles, and may be 
null alleles.  These two mutations are different since n1792 is 
suppressed by one copy of the amber suppressor sup-7(sb), while n2111 
is not suppressed.
The cells affected by lin-44 are related by their position in the 
tail and not by lineage, which suggests that cell-cell interactions 
play a role in controlling these asymmetric cell divisions.  In his 
studies of mab-9, Andrew Chisholm observed that when the B cell is 
killed in wild-type males, the polarities of the F and U cell lineages 
are reversed, just as they are in lin-44 animals.  This observation 
suggests that lin-44 may function in cell-cell signalling between B 
and F and U.  We are trying to determine which cells, if any, can 
influence the polarities of the B and T cells.  We have killed the B 
cell in wild-type L1 males and looked for effects on the polarity of 
the T cell lineage and have killed T in wild-type L1 males and looked 
for effects on B.  We have not seen an effect in either case.  
Furthermore we have killed the cell AB.prpaaaap, the mother of the B 
cell, in him-5 and lin-44; ryos and have not 
observed an effect in either case.  Since the B cell never existed in 
these animals, this result strongly indicates that B does not 
influence the polarity of T.  We are performing similar experiments by 
killing the T cells in the embryo before the B cell is born.  We have 
not observed an effect on the B cell in him-5 males.  Studies of lin-
44; e in progress.
Finally, we are cloning the lin-44 locus.  lin-44 maps about 0.1 m.u.
to the right of unc-73 I, which has been cloned in the laboratory of 
Joe Culotti .  The unc-73 clone identified a 1,100 kb contig.  We 
mapped two deficiencies that uncover lin-44, hDf6 and hDf7, to the unc-
73 contig by probing Southern blots of N2, hDf6 dpy-5 unc-13; hDp31,
and hDf7 dpy-5 unc-13; sDp2  DNA with labeled cosmids on the contig.  
By comparing band intensities between wild-type and deficiency-bearing 
strains, we determined whether a particular cosmid was under the 
deficiency.  We also looked for polymorphic bands in the deficiency 
strains, indicating a possible breakpoint.  From these experiments we 
have generated the physical map shown below.  We plan to isolate a 
clone containing the lin-44 gene by microinjection of cosmid or YAC 
DNA.
[See Figure 1]

Figure 1