tharris's lin-46 [17 articles]

Abstract

"In multicellular organisms cell fates are determined by a combination of spatial, temporal and sex-specific cues. The mechanisms by which the heterochronic genes regulate the temporal fates of cells are poorly understood. The post-embryonic development of hypodermal seam cells, which have distinct cell division pattern at each larval stage and terminally differentiate at the L4/adult switch, provides a model to study how developmental timing is regulated during animal development. A cascade of heterochronic genes have been identified that form a complex ...

Abstract

LIN-42, the Caenorhabditis elegans homolog of the Period (Per) family of circadian rhythm proteins, functions as a member of the heterochronic pathway, regulating temporal cell identities. We demonstrate that lin-42 acts broadly, timing developmental events in the gonad, vulva, and sex myoblasts, in addition to its well-established role in timing terminal differentiation of the hypodermis. In the vulva, sex myoblasts, and hypodermis, lin-42 activity prevents stage-specific cell division patterns from occurring too early. This general function of timing stage-appropriate cell division ...

Abstract

The C. elegans heterochronic genes program stage-specific temporal identities in multiple tissues during larval development. These genes include the first two miRNA-encoding genes discovered, lin-4 and let-7. We show that lin-58 alleles, identified as lin-4 suppressors, define another miRNA that controls developmental time. These alleles are unique in that they contain point mutations in a gene regulatory element of mir-48, a let-7 family member. mir-48 is expressed prematurely in lin-58 mutants, whereas expression of mir-241, another let-7 family member residing immediately ...

Abstract

The microRNA let-7 is a critical regulator of developmental timing events at the larval-to-adult transition in C. elegans. Recently, microRNAs with sequence similarity to let-7 have been identified. We find that doubly mutant animals lacking the let-7 family microRNA genes mir-48 and mir-84 exhibit retarded molting behavior and retarded adult gene expression in the hypodermis. Triply mutant animals lacking mir-48, mir-84, and mir-241 exhibit repetition of L2-stage events in addition to retarded adult-stage events. mir-48, mir-84, and mir-241 function together to ...

Abstract

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 ...

Abstract

The level of lin-28 activity is critical to the normal succession of diverse developmental events during the first three larval stages. If lin-28 activity is too low, the animal skips L2-specific events and develops precociously. If lin-28 is expressed continuously, the animal reiterates L2-specific events in later stages and retarded development results. The regulation of lin-28 expression occurs through the gene's 3'UTR. We identified a 15 nucleotide lin-4 complementary element that is required for lin-4 RNA to negatively regulate lin-28 expression ...

Abstract

We have isolated more than 40 alleles of sli-1 (suppressor of lineage defect) as silent suppressors of the Vulvaless (Vul) phenotype of weak alleles of let-23. sli-l mutations suppress the Vul, Male Abnormal and Lethal phenotypes of non-null alleles of let-23, but do not suppress the lethality of a null allele of let-23. Since these mutations are silent and do not suppress nulls, we believe that sli-l is a negative regulator of let-23, rather than a target of let-23 activity. Certain ...

Abstract

lin-4 and let-7 are founding members of an extensive class of genes with small noncoding RNA transcripts, termed microRNAs. microRNAs are 18-25 nucleotides long, and are generated by the processing of a 70-nucleotide hairpin precursor. Mutations in lin-4 and let-7 disrupt the timing of developmental programs, causing heterochronic defects. Mutation of the let-7 locus affects the developmental program that specifies the cell fates of the lateral hypodermis. let-7 retarded mutants undergo an extra molt, and terminal differentiation of the hypodermis is ...

Abstract

The heterochronic gene pathway is responsible for regulating the timing of stage specific developmental events. Genes in this pathway have been identified, such as lin-28 and lin-14, whose regulated expression denotes larval specific events. Loss-of-function mutations in these genes cause precocious phenotypes where certain cell divisions and differentiation are skipped. Alleles of lin-46, a heterochronic gene, were isolated as suppressors of the lin-28 precocious phenotypes. lin-46 null animals display an incomplete retarded phenotype at a low penetrance. lin-46 encodes a protein ...

Abstract

The daf-12 nuclear hormone receptor specifies L3 options of dauer formation and reproductive growth, and couples dauer and heterochronic pathways. Genetic analysis suggests that daf-12 is necessary for dauer diapause, but only partly required for the promotion of reproductive growth. As evidence, candidate null mutants of daf-12 have completely penetrant dauer defective phenotypes, but impenetrant delayed heterochronic phenotypes starting in the third larval stage. In contrast, recessive gain-of-function alleles are dauer defective and display penetrant heterochrony in gonadal and extragonadal tissues. ...

Abstract

The heterochronic gene pathway controls the timing of larval developmental events. Central to the action of this pathway is the developmental down-regulation of lin-14 and lin-28, whereby high levels specify L1 events, and lower levels specify L2 and L3 events. The decrease in lin-14 and lin-28 results from translational repression by the small RNA product of lin-4. lin-4 RNA is complementary to sequences in the 3' UTR of its target mRNAs, and recent experiments suggest that lin-4 acts by gating access ...

Abstract

Searching for downstream genes in the vulval induction pathway Andy Golden and Paul W. Sternberg, Caltech, Division of Biology and HHMI, Pasadena, CA 91125 The signalling pathway leading to vulval induction now contains a large number of conserved proteins with striking similarity to the signalling proteins used in yeasts, Drosophila, and mammals. The vulval induction pathway utilizes an EGF/TGF-alpha-like protein (lin-3), a receptor tyrosine kinase (let-23), an adaptor protein (sem-5), a ras protein (Zet-60), a raf kinase (lin-46), and a MAP ...

Abstract

The succession of developmental events in the C elegans larva is governed by the heterochronic genes. When mutated, these genes cause either precocious or retarded developmental phenotypes, in which stage-specific patterns of cell division and differentiation are either skipped or reiterated, respectively. We identified a new heterochronic gene, lin-46, from mutations that suppress the precocious phenotypes caused by mutations in the heterochronic genes lin-14 and lin-28. lin-46 mutants on their own display retarded phenotypes in which cell division patterns are reiterated ...

Abstract

The heterochronic genes control the succession of stage-specific developmental events in non-gonadal tissues of the larva. When one of these genes is mutant the animal shows either precocious or retarded heterochronic development. In heterochronic development, stage-specific patterns of cell division and differentiation are either skipped altogether or reiterated in subsequent stages. lin-46 mutations were isolated as recessive suppressors of precocious development. Animals carrying lin-28, lin-42, or certain lin-14 mutations develop normally when lin-46 is also mutant. lin-46 is therefore required for ...

Abstract

LIN-28 acts early in larval development to determine what developmental events happen in the L2 stage and later. LIN-46 acts antagonistically at a step immediately downstream of LIN-28. Our genetic analysis has revealed that LIN-46 independently affects cell fates at the L2/L3 transition and the larval-to-adult (L/A) switch. Thus, LIN-28 and LIN-46 converge at a branch-point in the heterochronic pathway. LIN-28 is a predominantly cytoplasmic protein that is present in complexes with non-polysomal mRNAs. LIN-28 is conserved in evolution to humans ...

Abstract

The heterochronic loci specify developmental age of various tissues and ensure the proper succession of temporal fates. We have been focusing on regulatory circuits that regulate third and later larval stage fates. The nuclear hormone receptor daf-12 specifies L3 options of reproductive growth and dauer formation. Null mutants of daf-12 are fully dauer defective, but have impenetrant delayed heterochronic phenotypes in gonadal and extragonadal tissues, suggesting that overlapping functions must work together with daf-12 to specify reproductive growth. In screens for ...

Abstract

The heterochronic genes of Caenorhabditis elegans encode part of a regulatory system that controls the temporal component of cell fates in development. The genes have been characterized genetically and molecularly, and their study has so far revealed a genetic hierarchy that specifies sequences of developmental events, a novel RNA-mediated mechanism of gene regulation and a reprogramming phenomenon associated with arrested development. ...