A Classical Model Organism-C. elegans

The diversity of organisms are formed in the process of evolution. Different organisms have different morphological structures and physiological characteristics, but the genes that have important functions for life activities are highly conserved. So organisms with the characteristics of a small individual, short reproductive cycle, easy to obtain, simple cultivation and convenient experimental operation are often used to perform science research to reveal certain universal law of life. These special and selected creatures are called model organisms. Model organisms have been playing an important role in the genetic research field.

Sydney Brenner first put C. elegans on use into the laboratory to study the genetic development process[1]. After that, C. elegans becomes a member of model organisms, and it contributes to many famous findings. In this article, we will introduce the hot model organism-C. elegans from the following aspects:

1. What is An C. elegans?
2. Why is C. elegans Widely Used in Various Research Fields?
● Simple Structure and Transparent Body
● Short Life Cycle and Fast Growth
● Easy to Culture in the Laboratory
● Both Hermaphrodite and Male
3. Important Research Results Related to C. elegans
● Programmed Cell Death
● The Discovery of the First miRNA
● RNA Interference
4. Recent Research of C. elegans

1. What is An C. elegans?
C. elegans, short for Caenorhabditis elegans, is a free-living nematode that lives in soil. The adult nematode is only 1mm long, transparent and feeds on bacteria. And it is not harmful to human because it is non-parasitical.

C. elegans is worm-like, symmetrical on both sides, and nonsegmented. C. elegans has a cuticle covering on the body surface, four main epidermal cords and a prosthetic body cavity filled with body fluids. C. elegans includes an oral, pharyngeal, intestinal, gonadal, and collagen cuticle, according to its basic anatomy. And C. elegans can be male or hermaphrodite.

2. Why is C. elegans Widely Used in Various Research Fields?
The scientists favor C. elegans due to its own superiority. Here list some primary advantages of C. elegans in the science research.

2.1 Simple Structure and Transparent Body
C. elegans is small in size, simple in structure and genome. C. elegans maintains a fixed number of somatic cells from an embryo to an adult. The hermaphrodite adult contains 959 individual cells, while the male adult is composed of 1031 individual cells. And it is the only organism in which all the cells of the body can be counted and classified. In addition, the transparency of C. elegans facilitates the observation and tracking of cell differentiation and other developmental processes in intact organisms.

2.2 Short Life Cycle and Fast Growth
C. elegans has a short life cycle, fast growth. These traits ensure that the nematode can reproduce in large numbers in the laboratory. It takes only four days to develop from a single fertilized egg into an adult that can lay eggs, which makes it possible to continuously observe and track the evolution of each cell. Hermaphrodite adults can lay about 300 fertilized eggs in their lifetime, or mate with male nematodes to produce as many as 1,000 offspring.

After hatching, the eggs undergo four larval stages (L1-L4). C. elegans can enter another larval phase that called dauer larva, when the environment is altered, such as populations are crowded or food is scarce. Dauer fights adversity and doesn't age. Hermaphrodite individuals produce sperm at the L4 stage and lay eggs at the adult stage. The adults can live about 15 days.

2.3 Easy to Culture in the Laboratory
First of all, C. elegans is small, with hundreds of nematodes growing in a 50 mm petri dish. Second, C. elegans only eats bacteria, and if a few worms are placed on a petri dish, a large number of offspring can be produced in a few days. Compared with mammalian cell culture, there is no need to artificially regulate CO2 concentration, as long as the temperature is well controlled, the nematodes grow well. Furthermore, C. elegans can be stored in a refrigerator at -80 ℃ or in liquid nitrogen. And they can continue to be studied after resuscitation, which greatly facilitates the preservation of abundant C. elegans strains of various genetic backgrounds.

2.4 Both Hermaphrodite and Male
In the natural state, most C. elegans individuals are hermaphrodite, only about one-thousandth of the population of males. But males can be produced by heat excitation in the laboratory. Because C. elegans has both male and hermaphroditic sex characteristics, they can be interbreeding or self-insemination. Self-insemination makes the new traits produced by mutation or interbreeding can be directly passed on to the next generation, which is an advantage not available to other model organisms. Studies on the frequency of overcrossing in natural populations show that self-crossing is the main way of C. elegans reproduction, and the incidence of infrequent overcrossing is very low[2][3].

3. Important Research Results Related to C. elegans
C.elegans worms are contributive to some significant research findings. Here list several major research achievement.

3.1 Programmed Cell Death
H. Robert Horvitz, at the United States, found "programmed cell death" by using C. elegans as a research target[4]. And He was also awarded the Nobel Prize in 2002 for the finding. Programmed cell death (PCD), also known as cell suicide, is any form of cell death mediated by intracellular procedures. PCD includes apoptosis and autophagy. Necrotic apoptosis has also been shown to be another form of programmed cell death[5].

3.2 The Discovery of the First miRNA
In 1989, Victor Ambros discovered that the gene lin-4 controls the development of C. elegans larvae by inhibiting the lin-14 gene. However, he thought the gene lin-4 expressed a regulatory protein that inhibited the expression of the gene lin-14. Until 1993, Victor's students Rosalind Lee and Phonda Feinbaum successfully cloned lin-4. They found that the product of lin-4 is not a protein-encoding mRNA, but a 22-nucleotide non-coding RNA containing several partially complementary sequences to the 3'UTR of lin-14 mRNA. They believed that this complementarity is responsible for inhibiting the translation of lin-14 mRNA into LIN-14 protein. Lin-4 RNA is the first miRNA found.

3.3 RNA Interference
In eukaryotes, there is a phenomenon that the expression of the gene is inhibited or silenced by RNA molecules with their homologous sequences. The regulatory mechanism is known as RNA interference (RNAi)[6][7]. RNAi sometimes inhibits mRNA translation, sometimes degrades mRNA, and even silences the promoter that directs mRNA transcription. So RNAi has become a powerful experimental tool, a simple way to study how organisms "turn off" specific gene expression. Andrew Fire and Craig C. Mello Shared the 2006 Nobel Prize in physiology or medicine for their work on RNA interference in nematode worms C. elegans[8]. Their finding was published in 1998.

4. Recent Research of C. elegans
● Studies led by a Princeton University-led team have shown that C. elegans worms which ingested pathogenic Pseudomonas aeruginosa (known as P14) quickly learned to avoid the bacterium, and their offspring could inherit this aversive behavior from them via a process called transgenerational epigenetic inheritance (TEI), but only for four generations. And the researchers also discovered that the P14-exposed worms could pass on the pathogen aversion to their offspring due to increased expression of daf -7, a ligand for TGF-β.

● When mitochondria lose their function, calcium will accumulate in cells, which activates enzymes that degrade collagen. Collagen participates in building the outer structure of the cells, so the degradation of collagen weakens the muscle. Recently, a research team at the universities of Exeter and Nottingham (UK) and Tohoku University in Japan, has uncovered that inhibiting the enzymes that degrade collagen by using experimental drugs can prevent muscle from declining in C. elegans. The finding may provide a potential therapy for muscle diseases caused by aging or some pathological cause.

In summary, C. elegans is a popular model organism with many special characteristics. And many significant and breakthrough research findings are discovered by the study of C. elegans. Although the medical conditions are now very mature, there are still many diseases with limited treatment and little effect. So scientists continue to study how these diseases are caused and how to treat them, and model organisms, not only C. elegans, are powerful experimental materials.



Reference:
[1]Sydney Brenner. The genetics of Caenorhabditis elegans [J]. Genetics. 1974, 77 (1): 71–94.
[2]Hodgkin, JA, Brenner, S. Mutations causing transformation of sexual phenotype in the nematode Caenorhabditis elegans [J]. Genetics. 1977, 86 (2 Pt. 1): 275–87.
[3]Barrière A, Félix MA. High local genetic diversity and low outcrossing rate in Caenorhabditis [4] elegans natural populations [J]. Current Biology. 2005, 15 (13): 1176–84.
Engelberg-Kulka H, Amitai S, et al. Bacterial Programmed Cell Death and Multicellular Behavior in Bacteria [J]. PLoS Genetics. 2006, 2(10): e135.
[5] Degterev, Alexei, Huang, Zhihong, et al. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury [J]. Nature Chemical Biology. 2005, 1 (2): 112–119.
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[8] Fire A, Xu S, et, al. Montgomery MK Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans [J]. Nature. 1998 Feb 19; 391(6669):806-11.