CGC1, a new reference genome for .

The original 100.3 Mb reference genome for , generated from the wild-type laboratory strain N2, has been crucial for analysis of since 1998 and has been considered complete since 2005. Unexpectedly, this long-standing reference was shown to be incomplete in 2019 by a genome assembly from the N2-derived strain VC2010.

Recompleting the genome.

was the first multicellular eukaryotic genome sequenced to apparent completion. Although this assembly employed a standard strain (N2), it used sequence data from several laboratories, with DNA propagated in bacteria and yeast. Thus, the N2 assembly has many differences from any available today.

CRISPR/Cas9 Methodology for the Generation of Knockout Deletions in .

The Gene Knockout Consortium is tasked with obtaining null mutations in each of the more than 20,000 open reading frames (ORFs) of this organism. To date, approximately 15,000 ORFs have associated putative null alleles. As there has been substantial success in using CRISPR/Cas9 in , this appears to be the most promising technique to complete the task.

Analysis of a lin-42/period Null Allele Implicates All Three Isoforms in Regulation of Caenorhabditis elegans Molting and Developmental Timing.

The Caenorhabditis elegans heterochronic gene pathway regulates the relative timing of events during postembryonic development. lin-42, the worm homolog of the circadian clock gene, period, is a critical element of this pathway. lin-42 function has been defined by a set of hypomorphic alleles that cause precocious phenotypes, in which later developmental events, such as the terminal differentiation of hypodermal cells, occur too early.

The C. elegans Hypodermis Couples Progenitor Cell Quiescence to the Dietary State.

The nutritional status of an organism can greatly impact the function and behavior of stem and progenitor cells [1]. However, the regulatory circuits that inform these cells about the dietary environment remain to be elucidated. Newly hatched C.

Caenorhabditis elegans period homolog lin-42 regulates the timing of heterochronic miRNA expression.

MicroRNAs (miRNAs) are small RNAs that regulate gene expression posttranscriptionally via the 3' UTR of target mRNAs and were first identified in the Caenorhabditis elegans heterochronic pathway. miRNAs have since been found in many organisms and have broad functions, including control of differentiation and pluripotency in humans. lin-4 and let-7-family miRNAs regulate developmental timing in C.

Developmental transitions in C. elegans larval stages.

Molecular mechanisms control the timing, sequence, and synchrony of developmental events in multicellular organisms. In Caenorhabditis elegans, these mechanisms are revealed through the analysis of mutants with "heterochronic" defects: cell division or differentiation patterns that occur in the correct lineage, but simply at the wrong time. Subsets of cells in these mutants thus express temporal identities normally restricted to a different life stage.

The C. elegans developmental timing protein LIN-42 regulates diapause in response to environmental cues.

Environmental conditions can have a major impact on developmental progression in animals. For example, when C. elegans larvae encounter harsh conditions they can reversibly halt the passage of developmental time by forming a long-lived dauer larva at the end of the second larval stage.

miRNAs give worms the time of their lives: small RNAs and temporal control in Caenorhabditis elegans.

Alteration in the timing of particular developmental events can lead to major morphological changes that have profound effects on the life history of an organism. Insights into developmental timing mechanisms have been revealed in the model organism Caenorhabditis elegans, in which a regulatory network of heterochronic genes times events during larval development, ensuring that stage-specific programs occur in the appropriate sequence and on schedule. Developmental timing studies in C.

miRNA regulation through ligand occupancy of a nuclear hormone receptor.

MicroRNAs (miRNAs) posttranscriptionally regulate gene expression, but the factors that direct transcription of miRNAs are not well characterized. Activation versus repression of key developmental miRNAs in Caenorhabditis elegans is directly mediated by ligand occupancy of a nuclear hormone receptor that acts to couple nutrient availability to developmental programs.

C. elegans DAF-18/PTEN mediates nutrient-dependent arrest of cell cycle and growth in the germline.

The molecular pathways that link nutritional cues to developmental programs are poorly understood. Caenorhabditis elegans hatchlings arrest in a dormant state termed "L1 diapause" until food is supplied. However, little is known about what signal transduction pathways mediate nutritional status to control arrest and initiation of postembryonic development.

Novel heterochronic functions of the Caenorhabditis elegans period-related protein LIN-42.

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.

Regulatory mutations of mir-48, a C. elegans let-7 family MicroRNA, cause developmental timing defects.

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.

Intrinsic and extrinsic regulators of developmental timing: from miRNAs to nutritional cues.

A fundamental challenge in biology is to understand the reproducibility of developmental programs between individuals of the same metazoan species. This developmental precision reflects the meticulous integration of temporal control mechanisms with those that specify other aspects of pattern formation, such as spatial and sexual information. The cues that guide these developmental events are largely intrinsic to the organism but can also include extrinsic inputs, such as nutrition or temperature.

Chromosome cohesion is regulated by a clock gene paralogue TIM-1.

Faithful transmission of the genome requires that a protein complex called cohesin establishes and maintains the regulated linkage between replicated chromosomes before their segregation. Here we report the unforeseen participation of Caenorhabditis elegans TIM-1, a paralogue of the Drosophila clock protein TIMELESS, in the regulation of chromosome cohesion. Our biochemical experiments defined the C.

The Caenorhabditis elegans hunchback-like gene lin-57/hbl-1 controls developmental time and is regulated by microRNAs.

Temporal control of development is an important aspect of pattern formation that awaits complete molecular analysis. We identified lin-57 as a member of the C. elegans heterochronic gene pathway, which ensures that postembryonic developmental events are appropriately timed.