4 elegans heterochronic lee lin pdf

Methods Citations. Results Citations. Figures and Topics from this paper. Citation Type. Has PDF. Publication Type. More Filters. A genetic mapping system in Caenorhabditis elegans based on polymorphic sequence-tagged sites.

We devised an efficient genetic mapping system in the nematode Caenorhabditis elegans which is based upon the differences in number and location of the transposable element Tc1 between the Bristol … Expand. A local, high-density, single-nucleotide polymorphism map used to clone Caenorhabditis elegans cdf The C. View 1 excerpt, cites background. Although the mature miRNA was strongly affected by lin activity, the transcriptional reporter was not.

It is also possible that lin utilizes a mechanism we do not yet understand, possibly acting on the RNA to decrease stability, rather than as a traditional transcription factor. This work also provides a possible explanation for the unusual nature of lin-4 mutants.

This work has uncovered the reason for this unusually catastrophic phenotype: removing lin-4 effectively removes five miRNAs from two different miRNA families from the heterochronic pathway. When lin-4 is mutated, lin is not down-regulated, meaning it continues repressing the expression of the 3let-7s and mir long after the L1 is over.

The combined loss of lin-4 , the 3let-7s , and mir is profound, committing the worm to executing L1-specific fates indefinitely. Supplemental material is available online at www. Communicating editor: D. National Center for Biotechnology Information , U.

Journal List Genetics v. Published online Nov 4. Mitchell A. Eric G. Author information Article notes Copyright and License information Disclaimer. E-mail: ude. Received Aug 19; Accepted Oct This article has been cited by other articles in PMC. Abstract In normal development, the order and synchrony of diverse developmental events must be explicitly controlled.

Keywords: C. Microscopy and phenotype analysis Nomarski DIC and fluorescence microscopy were used to count seam cell nuclei and score adult lateral alae. Protein extraction and Western blot Synchronous cultures were prepared by bleaching 5—10 cm plates of gravid adults for each strain according to standard protocols to isolate unhatched eggs Hope Data and reagent availability The authors state that all data necessary for confirming the conclusions presented in the article are represented fully within the article.

Results The 3let-7s act in the lin—lin feedback loop The 3let-7s act downstream of lin to regulate L2 specific cell fates: To assess the contribution of the 3let-7s to lin regulation, we employed a genetic background that lacked functional lin-4 , a known regulator of lin Table 1 The 3let-7s act downstream of lin in the heterochronic pathway.

Open in a separate window. Table 2 lin and hbl-1 are genetically downstream of the 3let-7s. LIN is constitutively expressed in the absence of the 3let-7s: Since the retarded phenotype seen in lin-4 e ; lin nts ; 3let-7s 0 animals required lin , we assayed for changes in LIN expression directly by immunoblot Figure 1.

Figure 1. Table 3 The 3let-7s repress expression of lin :: GFP. Table 4 mir acts downstream from lin in the heterochronic pathway. Figure 2.

LIN negatively regulates the 3let-7s and mir The promoter regions of the 3let-7s and mir contain putative LIN binding sites: lin encodes a sequence-specific DNA-binding transcription factor Hristova et al.

Figure 3. LIN mutations affect the timing of expression of the 3let-7s and mir transcriptional reporters: As a proxy for measuring the abundance of the primary transcripts of the 3let-7s and mir , we utilized a set of Pmir :: GFP reporters Martinez et al.

Figure 4. Discussion For many years we have known that lin positively regulates lin , but the mechanism underlying this regulation was unknown. Figure 5. Footnotes Supplemental material is available online at www. Literature Cited Abbott A. The let-7 microRNA family members mir, mir, and mir function together to regulate developmental timing in Caenorhabditis elegans. Cell 9 : — Cell 4 : — A hierarchy of regulatory genes controls a larva-to-adult developmental switch in C.

Cell 57 : 49— MicroRNAs and developmental timing. Heterochronic mutants of the nematode Caenorhabditis elegans. Science : — The lin locus of Caenorhabditis elegans controls the time of expression of specific postembryonic developmental events. Genes Dev. Temporal regulation of lin by the antagonistic action of two other heterochronic genes, lin-4 and lin LIN28 alters cell fate succession and acts independently of the let-7 microRNA during neurogliogenesis in vitro.

Development : — Mutations that lead to reiterations in the cell lineages of C. Cell 24 : 59— Cell : — A Caenorhabditis elegans homologue of hunchback is required for late stages of development but not early embryonic patterning. The timing of lin-4 RNA accumulation controls the timing of postembryonic developmental events in Caenorhabditis elegans. RNA 19 : — Oxford University Press, Oxford. Dauer larva quiescence alters the circuitry of microRNA pathways regulating cell fate progression in C.

The C. Cell 75 : — The microRNAs of Caenorhabditis elegans. The C elegans hunchback homolog, hbl-1, controls temporal patterning and is a probable microRNA target. Regulation of gene expression by alternative promoters. Mutations that lead to reiterations in the cell lineages of C. The cold shock domain protein LIN controls developmental timing in C. The bicoid protein determines position in the Drosophila embryo in a concentration-dependent manner.

Determination of the embryonic axes of Drosophila. Dev Suppl. Determination of spatial domains of zygotic gene expression in the Drosophila embryo by the affinity of binding sites for the bicoid morphogen.

Heterochronic mutations affecting shoot development in maize. The Caenorhabditis elegans heterochronic gene lin encodes a nuclear protein that forms a temporal developmental switch. The Drosophila anachronism locus: a glycoprotein secreted by glia inhibits neuroblast proliferation. Molecular genetics of the Caenorhabditis elegans heterochronic gene lin Heterochronic genes control cell cycle progress and developmental competence of C.

Mutation of protein kinase A causes heterochronic development of Dictyostelium. The timing of lin-4 RNA accumulation controls the timing of postembryonic developmental events in Caenorhabditis elegans. Gene expression patterns : GEP. View 5 excerpts, cites methods and background. The temporal patterning microRNA let-7 regulates several transcription factors at the larval to adult transition in C.

Developmental cell. Fish Physiology and Biochemistry. View 2 excerpts, cites background. A role for Lin in growth and metamorphosis in Drosophila melanogaster. Mechanisms of Development. View 1 excerpt, cites background. Highly Influenced. View 14 excerpts, cites background and results. Dynamic gene expression of Lin during embryonic development in mouse and chicken.

Mutations in the heterochronic gene lin of C.