Marx JL (1984) Science "New clues to developmental timing."

Marx JL

[Science, 1984]

Within the past few years researchers have finally begun to be able to peer inside a hitherto impenetrable black box, namely, the development of complex organisms. The genes that control the commitment of embryonic cells to specific fates are now being found and characterized. A case in point is reported in this issue of Science (p. 409). Victor Ambros of Harvard University and H. Robert Horvitz of Massachusetts Institute of Technology have identified genes that affect the timing of developmental events in the roundworm Caenorhabditis elegans.

Link CD (1988) Worm Breeder's Gazette "Call for C. elegans Cloned Genes"

Link CD

[Worm Breeder's Gazette, 1988]

A few years ago, when I was brewing up C. elegans and P. redivivus libraries, I also constructed a genomic lambda EMBL-4 library from a wild strain, WS9-6, that I had gotten from Victor Ambros. This male/female strain is morphologically similar to C. elegans, but is not cross-fertile with either C. elegans or C. remanei. This spring I am planning to fish some C. elegans genes out of this library as an exercise for a molecular genetics laboratory course. If anyone has a gene that they might like isolated from this library (for evolutionary comparisons, etc.) please let me know.

(2019) Development "The people behind the papers - Sungwook Choi."

[Development, 2019]

The control of timing in development is crucial, both within and between tissues. Heterochrony involves shifts in the rate of development of some tissues relative to others, and although the first heterochronic genes were identified in <i>Caenorhabditis elegans</i> in the early 1980s, their role in inter-tissue developmental coordination is still not completely understood. A new paper in Development tackles this problem with an analysis of the role of <i>lin-28</i>, a key heterochronic gene, in worm fertility. We caught up with Sungwook Choi, first author and recently graduated PhD student in Victor Ambros' lab at the University of Massachusetts Medical School in Worcester, to find out more.

Maatouk D et al. (2006) ScientificWorldJournal "MicroRNAs in development."

Harfe B, Maatouk D

[ScientificWorldJournal, 2006]

Over 10 years ago, the lab of Victor Ambros cloned an unusual gene, lin-4, which encodes two small RNA transcripts[1]. In the past few years, hundreds more of these tiny transcripts, termed microRNAs (miRNAs), have been uncovered in over a dozen species. The functions of the first two miRNAs, lin-4 and let-7, were relatively easy to identify since they were found in forward genetic screens in Caenorhabditis elegans[1,2,3]. However, uncovering the functions of the growing list of miRNAs presents a challenge to developmental biologists. This review will describe our current understanding of how miRNAs regulate gene expression and will focus on the roles these noncoding RNAs play during the development of both invertebrate and vertebrate species.

Hodgkin JA (1988) Worm Breeder's Gazette "informational suppression by male-abnormal mutations: new names, new data."

Hodgkin JA

[Worm Breeder's Gazette, 1988]

As previously reported (WBG 10-1: 112, 10-2: 30, etc.) mutations at six different loci act as allele-specific suppressors of mutations in a variety of genes: tra-2, unc-54, etc. These mutations also have characteristic morphological effects on the anatomy of the adult male tail and, to a lesser extent, of the hermaphrodite vulva. For this reason they have hitherto been assigned to the mab (male abnormal) gene category: mab-1, ed) and mab-12 through mab-16 (unpublished). However, they exhibit such a distinctive set of common properties that it has been decided (with the agreement of Andy Papp, Victor Ambros, Rock Pulak and Phil Anderson, who have been responsible for isolating most of these suppressor mutations) to assign them to a new gene

Sin, Olga et al. (2015) International Worm Meeting "Identification of MOAG-2/LIR-3 as a regulator of protein aggregation."

Guryev, Victor, Reinke, Valerie, Sin, Olga, Willinge Prins, Romeo, Wang, Hai Hui, Martineau, Celine, Mata Cabana, Alejandro, Seinstra, Renee, Nollen, Ellen, Kudron, Michelle, de Jong, Tristan

[International Worm Meeting, 2015]

Aging-related protein aggregation is one of the hallmarks of neurodegenerative disorders such as Alzheimer, Parkinson and polyglutamine diseases. The cellular processes that drive protein aggregation in these diseases have remained largely unknown. Using a genetic screen in a C. elegans model for polyglutamine aggregation, we here identified modifier of aggregation 2 (moag-2). Mutation or partial deletion in this gene decreased the number of aggregates in our model. Additionally, moag-2/lir-3 mutants reduce the amount of SDS-resistant aggregates without changing total polyglutamine expression levels. We discovered that the causative gene of moag-2 is lir-3. moag-2/lir-3 encodes a protein with a predicted nuclear localization signal and two non-canonical C2H2 domains, which are homologous to the transcription factor for RNA polymerase III. The molecular function of MOAG-2/LIR-3 is unknown. Chromatin immunoprecipitation followed by sequencing data revealed that MOAG-2/LIR-3 is preferentially bound to promoter regions of non-coding RNA, namely tRNAs and snoRNAs. The consensus DNA sequence to which MOAG-2/LIR-3 is bound to corresponds to Box A and Box B motifs, which are recognized by the RNA Polymerase III machinery to initiate tRNA and snoRNA transcription. In fact, MOAG-2/LIR-3 is positioned in the same binding positions as the RNA Pol III complex, further suggesting a role for LIR-3 in non-coding RNA transcription. We are currently performing total RNA sequencing to reveal whether the aggregation phenotype displayed by the MOAG-2/LIR-3 mutants can be due to imbalanced RNA metabolism. By unraveling the role of moag-2/lir-3 we hope to get insight into how cells cope with aggregation-prone proteins.

Victor L. Jensen et al. (2006) European Worm Meeting "A Potential DAF-16 Target Involved in Longevity"

David L. Baillie, Victor L. Jensen, Donald L. Riddle

[European Worm Meeting, 2006]

Victor L. Jensen1, David L. Baillie2, and Donald L. Riddle3. Genes differing in steady-state RNA levels between N2 and daf-2 adults and N2 dauer larvae were identified using Serial Analysis of Gene Expression (SAGE) databases. One gene, a putative transcription factor, was isolated from a screen for genes involved in longevity. The outcrossed knockout allele was shown to have extended longevity, ~3% Him and ~2% Vab phenotypes. The 1 kb of genomic sequence 5? of the confirmed transcription start site contains several possible DAF-16 binding sites. By using a series of truncated promoter sequences to drive GFP expression, possible in vivo activity for these DAF-16 binding sites was observed. One consensus site DBE (DAF-16 Binding Element) may act to repress transcription. This is in agreement with the SAGE data which shows down regulation of this transcription factor in the daf-2 background. In daf-2 mutants DAF-16 is activated and is required for extended longevity. Transcriptional targets and the DNA binding motif for the transcription factor will be elucidated, and its role in longevity will be characterized.

Winkenbach LP et al. (2019) RNA Biol "Todos Santos small RNA symposium."

Claycomb JM, Doser R, Pasquinelli AE, Winkenbach LP, Reed KJ, Phillips CM

[RNA Biol, 2019]

Worm biologists from the United States, Canada, and the United Kingdom gathered at the Colorado State University Todos Santos Center in Baja California Sur, Mexico, April 3-5, 2019 for the Todos Santos Small RNA Symposium. Meeting participants, many of whom were still recovering from the bomb cyclone that struck a large swath of North America just days earlier, were greeted by the warmth and sunshine that is nearly ubiquitous in the sleepy seaside town of Todos Santos. With only 24 speakers, the meeting had the sort of laid-back vibe you might expect amongst the palm trees and ocean breeze of the Pacific coast of Mexico. The meeting started with tracing the laboratory lineages of participants. Not surprisingly, the most common parental lineages represented at the meeting were Dr. Craig Mello, Dr. Gary Ruvkun, and Dr. Victor Ambros, whom, together with Dr. Andy Fire and Dr. David Baulcombe, pioneered the small RNA field. In sad irony, on the closing day of the meeting, participants were met with the news of Dr. Sydney Brenner's passing. By establishing the worm, <i>Caenorhabditis elegans</i>, as a model system Dr. Brenner paved the way for much of the research discussed here.

Nigon VM et al. (2017) WormBook "History of research on C. elegans and other free-living nematodes as model organisms."

Nigon VM, Felix MA

[WormBook, 2017]

The nematode Caenorhabditis elegans is now a major model organism in biology. The choice of Sydney Brenner to adopt this species in the mid-1960s and the success of his team in raising it to a model organism status have been told (http://www.wormbook.org/toc_wormhistory.html; Brenner, 2001; Ankeny, 2001). Here we review the pre-Brenner history of the use of free-living nematodes as models for general questions in biology. We focus on the period that started in 1899 with the first publication of Emile Maupas mentioning Rhabditis elegans and ended in 1974 with the first publications by Brenner. A common thread in this period, aided by the variety in modes of reproduction of different nematode species, is found in studies of meiosis, fertilization, heredity and sex determination. Maupas in his 1900 opus on reproduction already chooses C. elegans as the species of reference. Hikokura Honda determined its hermaphrodite chromosomal content in 1925. C. elegans was again isolated and chosen as main subject by Victor Nigon in the 1940-50s. Nigon mastered crosses between C. elegans hermaphrodites and males, described the meiotic behavior of chromosomes in XX hermaphrodites and X0 males and, using tetraploids, correctly inferred that sex was determined by X chromosome to autosome dosage. With Ellsworth Dougherty, Nigon isolated and studied a C. briggsae body size mutant and a C. elegans slow growth mutant. Dougherty and his team devoted most of their work to finding a defined culture medium to screen for physiological mutants, focusing on C. briggsae. With Helene Fatt, Dougherty also performed the first genetic study of natural variation in C. elegans, concerning the difference in heat resistance of the Bergerac and Bristol strains. Jean Brun, a student of Nigon, performed a long and remarkable experiment in acclimatization of C. elegans Bergerac to higher temperatures, the significance of which remains to be clarified.

Adamczyk, Magdalene et al. (2010) C. elegans: Development and Gene Expression, EMBL, Heidelberg, Germany "Cell cycle control of VPC fate specification by regulation of EGFR/RAS/MAPK and NOTCH crosstalk"

Nusser, Stefanie, Adamczyk, Magdalene, Fisher, Jasmin, Hajnal, Alex

[C. elegans: Development and Gene Expression, EMBL, Heidelberg, Germany, 2010]

Caenorhabditis elegans vulval development is an excellent model to investigate the temporal and spatial regulation of cell fate specification in response to intercellular signals. During vulval development, three out of six equivalent vulval precursor cells (VPCs) adopt one of the two vulval fates. The central VPC P6.p expresses the primary (1) fate, induced by a signal from the gonadal anchor cell via the EGFR/RAS/MAPK pathway. The neighboring VPCs P5.p and P7.p adopt the secondary (2) fate in response to NOTCH-mediated lateral signaling. Thus, the crosstalk between LET-23/EGFR and LIN-12/NOTCH signaling determines cell fate patterning of the VPCs. Those signals must act at defined development al stages, hence temporal or cell cycle control might be important for cell fate specification. Victor Ambros showed in 1999 that the specification of the 1 fate in P6.p via LET-23/EGFR and the inhibition of the 1 fate in the neighboring cells occur prior to completion of the S phase, while 2 fate specification only occurs after S phase. The inhibition of the 1 fate is mediated via LIN-12/NOTCH target genes such as the MAPK phosphatase lip-1 or the lst genes. So far, only genes mediating the inhibitory function of LIN-12/NOTCH have been described. To identify late LIN-12/NOTCH targets instructing the 2 fate, we are arresting P5.p and P7.p in the G1 phase by a constitutive expression of the cyclin-dependent kinase inhibitor cki-1 . Different 2 cell fate markers will be analyzed for altered expression in arrested VPCs. Additionally, we will examine the downregulation of LET-23::GFP in arrested secondary cells. Our preliminary findings suggest a link between cell cycle progression and the temporal coordination of cell fate specification among equivalent cells.