The development of the small soil nematode Caenorhabditis elegans involves an invarient and precisely known temporal pattern or sequence of cell divisions and differentation events. The long term goal of this work is to elucidate how this temporal schedule of development is genetically encoded. The general questions to be addressed are: 1) What are the roles of individual genes in controlling temporal sequences of developmental events? 2) What are the tissue- and stage-specificities of those genes? 3) What are the relative roles of genes encoding cell-intrinsic vs cell-extrinsic functions in elaborating and interpreting temporal information during development? 4) How do these genes functionally interact among themselves and with genes controlling basic cellular processes such as cell division and differentiation? The genetic and phenotypic properties of mutants with altered temporal patterns of development (""""""""heterochronic mutants"""""""") will be studied in detail. An attempt will be made to identify by mutation all genes involved in controlling and executing a specific temporal switch in cell fate - the switch from larval programs (cell division and larval cuticle synthesis) to adult program (adult cuticle synthesis) for hypodermal """"""""seam"""""""" cells. For each newly identified gene, and for certain of the eight previously identified genes affecting this switch, detailed genetic analysis will be applied to determine their respective null phenotypes and thus their roles in wild-type development. Functional interactions will be explored by constructing multiply-mutant strains with known genetic lesions in two or more hetero-chronic genes. Temperature shift experiments using temperature-sensitive alleles will be used to investigate the time of action of each gene. Additional mutants will be sought defective specifically in the timing of postdauer development. Genetic analysis of genes so identified will be carried out. Genes transcribed stage- specifically, and/or specifically during either postdauer or nondauer development will be identified by probing recombinant phage libraries with cDNA probes. The sequences of these genes will be used to analyze the effects of heterochronic mutations on the expression of genes involved in specific developmental programs.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM034028-04
Application #
3284409
Study Section
Genetics Study Section (GEN)
Project Start
1984-07-01
Project End
1992-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Arts and Sciences
DUNS #
071723621
City
Cambridge
State
MA
Country
United States
Zip Code
02138
Ambros, Victor; Ruvkun, Gary (2018) Recent Molecular Genetic Explorations of Caenorhabditis elegans MicroRNAs. Genetics 209:651-673
McJunkin, Katherine; Ambros, Victor (2017) A microRNA family exerts maternal control on sex determination in C. elegans. Genes Dev 31:422-437
Ren, Zhiji; Veksler-Lublinsky, Isana; Morrissey, David et al. (2016) Staufen Negatively Modulates MicroRNA Activity in Caenorhabditis elegans. G3 (Bethesda) 6:1227-37
Burke, Samantha L; Hammell, Molly; Ambros, Victor (2015) Robust Distal Tip Cell Pathfinding in the Face of Temperature Stress Is Ensured by Two Conserved microRNAS in Caenorhabditis elegans. Genetics 200:1201-18
Ren, Zhiji; Ambros, Victor R (2015) Caenorhabditis elegans microRNAs of the let-7 family act in innate immune response circuits and confer robust developmental timing against pathogen stress. Proc Natl Acad Sci U S A 112:E2366-75
Sterling, Catherine H; Veksler-Lublinsky, Isana; Ambros, Victor (2015) An efficient and sensitive method for preparing cDNA libraries from scarce biological samples. Nucleic Acids Res 43:e1
Zinovyeva, Anna Y; Veksler-Lublinsky, Isana; Vashisht, Ajay A et al. (2015) Caenorhabditis elegans ALG-1 antimorphic mutations uncover functions for Argonaute in microRNA guide strand selection and passenger strand disposal. Proc Natl Acad Sci U S A 112:E5271-80
Harandi, Omid F; Ambros, Victor R (2015) Control of stem cell self-renewal and differentiation by the heterochronic genes and the cellular asymmetry machinery in Caenorhabditis elegans. Proc Natl Acad Sci U S A 112:E287-96
Nelson, Charles; Ambros, Victor; Baehrecke, Eric H (2014) miR-14 regulates autophagy during developmental cell death by targeting ip3-kinase 2. Mol Cell 56:376-88
Zinovyeva, Anna Y; Bouasker, Samir; Simard, Martin J et al. (2014) Mutations in conserved residues of the C. elegans microRNA Argonaute ALG-1 identify separable functions in ALG-1 miRISC loading and target repression. PLoS Genet 10:e1004286

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