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Comments on EG Moss et al. (1999) International C. elegans Meeting "The heterochronic gene lin-46 encodes a non-essential member of the moeA family and may be a target of lin-28 regulation" (0)
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EG Moss, RC Lee, JE Johnstone, D Au Yeung, & V Ambros (1999). The heterochronic gene lin-46 encodes a non-essential member of the moeA family and may be a target of lin-28 regulation presented in International C. elegans Meeting. Unpublished information; cite only with author permission.
The heterochronic genes lin-14 and lin-28 coordinate the timing of developmental events in early larval stages. If either activity is reduced then precocious expression of L3-specific events occurs in the L2. Because these genes act in diverse cell types to control a variety of cell division and differentiation events, they may act on diverse targets or on just a few that in turn have diverse affects. Mutations in lin-46 completely suppress lin-28 loss-of-function alleles and lin-14 hypomorphs. To our surprise, null mutations in lin-46 suppress null mutations in lin-28 to the wildtype phenotype. This immediately raises two questions: Might lin-46 be one of several targets of lin-28 ? and What can lin-46 tell us about the relationship between lin-14 and lin-28 ? Several experiments have delivered more questions than answers. By GFP fusion assay, lin-46 appears to be expressed exclusively in two bilaterally symmetric AV interneurons and this expression is not temporally regulated. This is in contrast to lin-14 and lin-28 , which are expressed ubiquitously in the L1 and then repressed. A precocious phenotype can result from lin-46 trangenes in a wildtype background, indicating that the level of lin-46 is important in heterochronic regulation. lin-46 mutations can suppress all alleles of lin-28 , hypomorphs of lin-14 , but not null alleles of lin-14 . Mutant combinations suggest that lin-46 does not act by raising the level of an activity upstream of lin-14 or lin-28 . Curiously, a lin-46 mutation appears unable to suppress the double mutant lin-42 ; lin-14(ts) , two mutations it can suppress separately, suggesting there is an important relationship among these genes. lin-46 encodes a member of the moeA family, which includes vertebrate gephyrin and a molybdopterin synthesis pathway component. These homologies suggest nothing more than the LIN-46 protein may interact with other proteins to carry out its function. Perhaps LIN-46 is a component of a multi-protein complex, whose components are targets of lin-28 negative regulation, so that a null mutation in lin-46 can reduce the output of the pathway without eliminating it.