Worm Breeder's Gazette 10(3): 119

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lin-43, A New Cell Cycle Gene?

Susan Euling and Victor Ambros

In our screens for new heterochronic mutants, we have isolated an 
interesting class of mutants which appear to have cell cycle defects.  
One such mutant, ma103, is a thin sterile mutant with a protruding 
vulva which lacks regions of adult alae.  ma103 was isolated from an 
EMS mutagenesis and defines the gene lin-43 I.  It maps approximately 
1 m.u.  to the left of dpy-5.  Aspects of its phenotype suggest that 
lin-43 belongs to the group of cell cycle mutants including lin-5 (
blocked in nuclear division), lin-6 (blocked DNA synthesis), and unc-
59 and unc-85 (blocked in cytokinesis).  Mutations in lin-43 appear to 
be blocked in one or more steps of the cell cycle that are required 
for both cell division and differentiation.
Defects in the hypodermal cell lineage of ma103 animals are variable 
and first observed after the L2 stage.  Beginning in the L3, some seam 
cells adopt an abnormal morphology.  In contrast to wild-type seam 
cells, the nucleus of these hypodermal cells is round, often has a 
raised appearance or crinkled borders.  While such cells can look 
'sick', they do not take on the appearance characteristic of a cell 
undergoing programmed cell death.  These abnormal looking seam cells 
are not observed to undergo nuclear division.  There seems to be a 
general failure of seam cell division in the L3 and L4 stages in lin-
43 animals.  Some seam cells, particularly those in the head, are 
displaced relative to seam cells in wild-type.  The defect in lin-43 
could be similar to lin-5, although nuclear breakdown which does occur 
in lin-5, is not been observed in lin-43.lin-43 mutants do not have 
complete adult lateral alae.  The majority of animals have patches of 
adult alae and some have no adult alae.  The regions of hypodermis 
which lack alae nevertheless often do contain seam cells, although 
some of these seam cells appear morphologically abnormal as described 
above.  Therefore, seam cell differentiation at the L4 molt as well as 
nuclear division at the L3 molt appears to be blocked in lin-43 
animals.
Vulva and gonad development of lin-43 mutants are also variably 
abnormal.  The time between molts and the time required for gonad 
morphogenesis is increased relative to wild type.  We have not 
observed the mutant gonad cell lineage in detail, but gonad 
development appears severely slowed or completely inhibited.  In 
approximately 65% of the adult mutant gonads, neither arm reflexes.  
Approximately 10% of the mutant animals are bivulva, and often the 
gonad and/or intestine is extruded.  Despite the overall sick 
appearance of lin-43 mutants, they undergo 4 molts and survive to the 
adult.  Although it was isolated in a screen for heterochronic mutants 
(protruding vulva and defective adult alae), lin-43 is not 
heterochronic.
Due to the general phenotypic similarities among lin-43, 
lin-6, ssible 
that lin-43 mutants could also be defective in some aspect of the cell 
cycle.  Further lineage analysis is necessary in order to determine 
the particular cell cycle event(s) in which lin-43 animals are 
defective.  Further genetic analysis is required to determine whether 
ma103 represents the null phenotype of lin-43.NOTE: If you isolate any 
sterile mutants with protruding vulvae and/or incomplete adult alae 
and are not interested in them, please send us their sibs.  Thanks.