Kreeger KY (1996) The Scientist "Hot papers: Programmed cell death."

Kreeger KY

[The Scientist, 1996]

Biologist H. Robert Horvitz discusses the genetics of cell death in the nematode C. elegans.

Thomas JH et al. (1994) Worm Breeder's Gazette "lin-36, a Class B Synthetic Multivulva Gene, Encodes a Novel Protein"

Thomas JH, Horvitz HR

[Worm Breeder's Gazette, 1994]

lin-36, a Class B Synthetic Multivulva Gene, Encodes a Novel Protein Jeffrey H. Thomas and H. Robert Horvitz, HHMI, Dept. Biology, MIT, Cambridge, MA 02139, USA

Goff SP (1999) Cancer Research "Genetic control of programmed cell death in the nematode Caenorhabditis elegans - Introduction."

Goff SP

[Cancer Research, 1999]

It is an honor and a great pleasure to introduce Dr. Robert Horvitz to you as the 1998 recipient of the Alfred Sloan Prize of the General Motors Cancer Research Foundation. Let me begin by telling you a little bit about Bob's

Gandhi, Jay et al. (2021) MicroPubl Biol

Fernandez, Anita G., Gandhi, Jay, Crosio, Giulia

[MicroPubl Biol, 2021]

Most cellular processes require the coordinate activities of multiple gene products. These collaborations vary with different contexts. mel-28 encodes a conserved multi-functional nucleoporin required for nuclear envelope integrity, the post-mitotic rebuilding of the nuclear pore, and the proper segregation of chromosomes during mitosis (Galy et al. 2006; Fernandez and Piano 2006). Loss of mel-28 results in strict maternal-effect embryonic lethality. Thus homozygous mutant embryos produced from heterozygous mothers show typical wild-type development until they become adults and produce normal-sized broods of inviable embryos. This suggests that mel-28 is required for embryonic development but is dispensable for post-embryonic development and adult processes such as fertility. To identify genes that function collaboratively with mel-28, we did an RNAi screen to find genes that cause fertility defects in mel-28 mutant animals but not wild-type animals (Fernandez et al. 2014). Among the genes identified were those encoding components of the minus-end-directed microtubule motor dynein.

Chen X et al. (2015) Mol Neurodegener "Erratum to: Ethosuximide ameliorates neurodegenerative disease phenotypes by modulating DAF-16/FOXO target gene expression."

McCue HV, Chen X, Morgan A, Kashyap SS, Barclay JW, Kraemer BC, Burgoyne RD, Wong SQ

[Mol Neurodegener, 2015]

The original version of this article [1] unfortunately contained a mistake. The author list contained a spelling error for the author Hannah V. McCue. The original article has been corrected for this error. The corrected author list is given below:Xi Chen, Hannah V. McCue, Shi Quan Wong, Sudhanva S. Kashyap, Brian C. Kraemer, Jeff W. Barclay, Robert D. Burgoyne and Alan Morgan

Kim, Seongseop et al. (2015) International Worm Meeting "An atlas of G protein-coupled neurotransmitter and neuropeptide receptor expression patterns in C. elegans."

Fernandez, Robert, Koelle, Michael R., Pepper, Judy, Kim, Seongseop

[International Worm Meeting, 2015]

Many neurotransmitters and neuropeptides signal by activating G protein-coupled receptors (GPCRs), but there is a limited understanding of the biological purpose of such signaling in large part because there are mutant phenotypes for only a tiny fraction of the GPCRs. The few C. elegans GPCRs that have been studied in detail are expressed in a very limited number of cells, and mutants show very specific defects in the behaviors controlled by those cells. Although it is now possible to get knockout mutations for any receptor, it has not been possible to identify any defects since we do not know what very specific defects to look for. If we knew the expression patterns for all the neural GPCRs, then we could analyze in detail knockouts of just the GPCRs expressed within the circuit that controls a behavior of interest for specific defects in that behavior. This strategy would provide a path to finally understand the functions of neurotransmitter/neuropeptide signaling through GPCRs.We are analyzing the cellular expression patterns of the ~100 neuropeptide receptor homologs and ~23 GPCRs for small molecule neurotransmitters that are found in C. elegans. We are using C-terminal translational gfp fusion transgenes generated by Sarov et al. (2012). These fosmid-based transgenes contain long stretches of 5' and 3' regulatory sequences and thus should show accurate and complete expression patterns. We are generating high-copy transgenes by microinjection to get bright GFP expression and also to generate possible over-expression phenotypes. We identify GFP-expressing cells by confocal microscopy, using several RFP transgenes to label specific cells as landmarks.Our pilot experiments have confirmed and added to previously known expression patterns of several neurotransmitter receptors. For example, our egl-6::gfp fosmid transgene showed expression in the HSN and GLR cells, as did a smaller transgene used by Ringstad and Horvitz (2008). However our fosmid transgene also showed additional expression in head, vulval, anal sphincter muscles, the gonadal sheath cells, and several additional neurons.Our receptor expression atlas will help identify neurotransmitter signaling events in all neural circuits, but we will first demonstrate its utility by focusing on the egg-laying circuit. This circuit consists of just four cell types, and we hope to identify all the neurotransmitter receptors that act in this circuit and to characterize their functions in generating the pattern of activity by which this circuit controls egg-laying behavior.

Casey DL (1999) Human Genome News "International team delivers C. elegans sequence."

Casey DL

[Human Genome News, 1999]

For the first time, scientists have the nearly complete genetic instructions for an animal that, like humans, has a nervous system, digests food, and reproduces sexually. The 97-million-base genome of the tiny roundworm Caenorhabditis elegans was deciphered by an international team led by Robert Waterston and John Sulston. The work was reported in a special issue of the journal Science (December 11, 1998) that featured six articles describing the history and significance of the accomplishment and some early sequence-analysis results.

Collins, Kevin et al. (2015) International Worm Meeting "Competing activation and inhibition in the Caenorhabditis elegans egg-laying behavior circuit."

Bode, Addys, Fernandez, Robert, Tanis, Jessica, Creamer, Matt, Collins, Kevin, Koelle, Michael

[International Worm Meeting, 2015]

Our fundamental goal is to understand how neurons communicate in circuits to establish an appropriate level of activity that produces a robust, stable behavior. Our approach is to analyze in detail the C. elegans egg-laying behavior circuit. We have developed GCaMP Ca2+ reporters, optogenetic, and chemical tools that allow us to record and manipulate activity in the HSNs, VCs, uv1s, and vulval muscles in freely behaving animals. We can clearly see rhythmic Ca2+ transients at the large (~10microm) HSN and VC presynaptic termini. The serotonergic HSNs show continuous rhythmic activity with each body bend punctuated by short (~3 minute) periods of inactivity that follow egg-laying events. In contrast, the cholinergic VCs only show activity during egg-laying events. Optogenetic activation of the HSNs is sufficient to induce VC neuron and vulval muscle activity that allows egg release. Acute silencing of the VCs using histamine-gated chloride channels decreases this response. Unlike for the HSNs, optogenetic activation of the VCs is unable to drive vulval muscle contraction and egg laying. Because we only see VC activity during the egg-laying active phase, we will test how acute optogenetic activation of the VCs modulates the vulval muscle serotonin response. Together, our results show that the HSNs act as a command motor neuron to initiate the egg-laying active phase and suggest that the VCs have more complex regulatory functions in the circuit. What turns the egg-laying circuit off? We found that release of eggs through the vulva deforms the tyraminergic uv1 cells, triggering a Ca2+ transient that may signal egg release. Optogenetic activation of the uv1 cells during an active phase blocks subsequent egg laying events. We are testing a model where released tyramine signals through the LGC-55 tyramine-gated chloride channel to inhibit HSN activity. Exogenous tyramine inhibits egg-laying behavior, this response is lost in lgc-55 mutants, and this defect can be rescued through re-expression of lgc-55 in the HSNs. We find that optogenetic activation of the uv1 cells blocks subsequent egg-laying events, and we are presently testing whether this inhibition is lost in tdc-1 and lgc-55 mutants defective for tyramine signaling. This would show that uv1 releases tyramine that signals through the LGC-55 receptor to terminate the active phase. Together, our results suggest the uv1 cells provide mechanosensory feedback of successful egg release, driving acute cessation of HSN activity to terminate the active phase.

Brownlee DJA et al. (1996) Parasitol Today "Nematode neuropeptides: Localization, isolation and functions."

Holden-Dye L, Brownlee DJA, Walker RJ, Fairweather I

[Parasitol Today, 1996]

Historically, peptidergic substances (in the form of neurosecretions) were linked to moulting in nematodes. More recently, there has been a renewal of interest in nematode neurobiology, initially triggered by studies demonstrating the localization of peptide immunoreactivities to the nervous system. Here, David Brownlee, Ian Fairweather, Lindy Holden-Dye and Robert Walker will review progress on the isolation of nematode neuropeptides and efforts to unravel their physiological actions and inactivation mechanisms. Future avenues for research are suggested and the potential exploitation of peptidergic pathways in future therapeutic strategies

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.