User:Abland8/sandbox

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Caenorhabditis elegans is a transparent nematode that can be found in soil environments.[1] C. elegans goes through a short life cycle that contains four larval stages, followed by a final adult stage. C. elegans can be either a hermaphrodite, or have separate female and male forms.[2] C. elegans displays holoblastic cleavage and is a unsegmented pseudocoelomate organism.[3] Fertilization is internal and the sperm entry helps determine the anterior-posterior axis. Formation of the gut within the organism occurs after the 28th cell stage.[4] The cortical PAR genes are crucial in axis determination.[5] C. elegans is also known to be a model organism. One of the advantages to using this species is that it possesses similar developmental signaling to humans. During development C. elegans goes through four stages called fertilization, cleavage, gastrulation, and neurulation. The organism also goes through postnatal development. These stages along with axis signaling make up the developmental life cycle of C. elegans.

Life Cycle[edit]

The C. elegans life cycle has an embryonic stage, a set of four larval stages and an adult stage.[6]  Embryonic development takes place over a period of 14 hours. First, the C. elegans embryos are left to hatch. After hatching, the larval stage begins. Within the larval stage, there are four molts that take place in order for the organism to enter the adult stage. Depending on the amount of resources in the environment, the larva may enter a dauer larval stage, in which they can stay for several months until conditions improve. It takes 13 hours to enter the dauer larval stage and if the C. elegans larva does not enter the dauer stage, then it will continue to the second larval stage after 12 hours. Following the 2nd larval stage, it takes 8 hours to for the larva to enter the 3rd larval stage. Whether in the dauer stage, or 3rd stage, the C. elegans enters a fourth larval stage that lasts 10 hours after which the organism begins to enter adulthood.

During the development of the embryo following fertilization, two meiotic divisions take place and the cytoplasm that was within the cell moves towards the posterior and the cortical cytoplasm is moved to the anterior region[6].  After cleavage continues, and the cells continue to divide, gastrulation begins to take place. Gastrulation is marked by the stage where two cells move into the interior as part of the invagination process. The lifespan of C. elegans lasts 2-3 weeks, with a generation time of 3-4 days and begins with fertilization.

Fertilization[edit]

The first part of the life cycle of C. elegans is fertilization. The fertilization process in C. elegans occurs internally and begins with an amoeboid sperm cell that has no flagellum. The sperm enters from any part of the outer surface of the oocyte[2].  While the point of entry of the sperm is known to be random, it later determines the posterior of the zygote. In C. elegans that contain hermaphrodite oocytes, the mature oocyte goes through ovulation and travels to the spermatheca. This results in fertilization.

When fertilization takes place in the hermaphrodite C. elegans, the process begins near either the intestine or anus portion of the worm. The oocytes mature in a single file line depending on their stages in development. They are formed by budding from the syncytial gonad[2]. Every oocyte bud that is created contains one nucleus and the oocytes are fertilized once they enter the spermatheca. After passing through the spermatheca, the embryos develop in the uterus and get discharged through the vulva. Another route of fertilization occurs when a male inseminates a hermaphrodite. The male sperm found in C. elegans is used to fertilize oocytes.[2] The sperm of the C. elegans consists of a nucleus with mitochondria tightly packed around it. After fertilization occurs and an embryo is produced, it begins to undergo cellular division to continue to the next stage of the life cycle called cleavage.

Cleavage[edit]

In C. elegans cleavage is rotational, holoblastic, and starts with the formation of 4 founder cells. The cell division in C. elegans is asymmetrical, which means that during the first cleavage the cleavage furrow is located asymmetrically along the axis of the egg. Axis determination in C. elegans is determined by elongated axis found during cell division. The decision of which end of the cell will become anterior or posterior is determined by which end the sperm cell enters the egg.[4] The cleavage furrow forms two cells called the AB cell, which is divided in an anterior AB and posterior AB, and a P1 cell. Next the embryo divides again, and the anterior AB cell divides longitudinal to the anterior-posterior axis while the P1 cell divides transverse to the axis. When these two divide a P2 cell and an embryonic founder cell are produced.[4]

Gastrulation in C. elegans embryo

Gastrulation[edit]

Gastrulation in C. elegans starts early compared to other organisms, it begins just after the formation of the P4 generation in 24-cell embryos.[7] Cell movement begins when two epidermal cell precursors Ea and Ep migrate from the surface of the embryo into the blastocoel.[8] The inward migration of Ea and Ep cells creates a tiny blastopore. As ingression occurs Ea and Ep ingress and their apical surfaces separate from the envelope and are covered by six cells. These six cells consist of 3 MS cells, 2 AB progeny cells, and a P4 cell.[9] After endodermal cells have completed ingression, mesodermal cells go through the same process and are followed by germ cells.[10] Ingressing cells accumulate non-muscle myosin at the apical surface when ingression happens and when ingression is finished myosin accumulates at the surface and undergoes a morphogenic change called apical constriction. During apical constriction the width of the apical surface decreases, this changes the shape of the cell.[11]

After the 28 cell stage, 2 daughter cells will migrate from the ventral side of C. elegans into the center of the embryo. When this occurs they will divide and cause the formation of a gut consisting of 20 cells.[4] The internalization of surface cells is important during the process of gastrulation as well as in neurulation.[12]

Neurulation[edit]

Neurulation is the stage in which the nervous system begins development following gastrulation. The beginning of neurulation occurs when the cells that will later make up the nervous system become internalized.[13] The cells of the ventral epidermis begin invagination into the gastrula and division occurs in order to produce neuroblasts.[14] The ventral surface of the embryo is comprised mainly of neuroblasts at this point and the neuroblasts continue to undergo division. The neuroblasts then form organized groups of cells within the embryo to create the structure of the nervous system. A structure called the ring ganglion or nerve ring functions as a brain in C. elegans as the organism has no synapses or network of nerves.[15] Following the last round of divisions of the neuroblasts, the surface of the embryo begins to be covered by the hypodermis that makes up the chitinous outer layer of C. elegans.[16] The end of neurulation is called the comma stage which occurs 300 minutes after the beginning of fertilization.[17]

Axis Signaling[edit]

Anterior-posterior signaling in C. elegans

Anterior/Posterior Axis[edit]

The determination of the anterior-posterior axis in C. elegans begins during fertilization. When sperm enters the oocyte, cytoplasmic movements cause the sperm pronucleus to migrate to one end .[18] The end that the sperm pronucleus migrates to becomes the posterior while the end opposite the sperm pronucleus becomes the anterior. After this process cortical rearrangement occurs and P-granules migrate to the posterior of the embryo. PAR proteins are distributed asymmetrically and are essential for the correct distribution of P-granules throughout the embryo. These proteins are also needed for interaction with actin filaments and to form them correct arrangement of the mitotic spindles. PAR-1 and PAR-2 proteins are expressed in the posterior portion of embryo while PAR-3 and PAR-6 are expressed the anterior. Both of these are present following the first mitotic division of the C. elegans embryo.[5][4] The P2 cell uses Wnt to signal the endomesodermal cell to divide along the anterior-posterior axis.[19]

Dorsal/Ventral Axis[edit]

The dorsal-ventral axis of C. elegans is formed following the division of the embryonic founder cell, also called the AB cell, during cleavage.[20] The dorsal/ventral axis is determined following the second mitotic division when the AB cell changes the orientation of the mitotic spindle.[21][5] Because the outer shell of the C. elegans embryo does not allow for enough space during division, the arrangement of the daughter cells leads to the formation of the dorsal-ventral axis. When the cell divides, it becomes elongated allowing the two AB daughter cells to form in the anterior and posterior positions.[5] The posterior AB cell, which is over the endomesodermal precursor cell (EMS), forms the dorsal axis. The two AB cells are controlled by signaling from Notch.[22] The EMS cell will become the ventral portion of the embryo. Two maternal genes apx-1 and glp-1 are used to determine the AB posterior and Ab anterior cell fates during cleavage.[23]

Left/Right Axis[edit]

While the exact mechanisms involved in the development of the left-right axis are not known, it is hypothesized that when the endomesodermal precursor cell divides and a mesodermal precursor is formed, half of the divided anterior AB cells receive signals while the other half do not.[22] This leads to differentiation between the two sides forming the left and right axis. Correct attachment of mitotic spindles is also needed in the cortex of the embryo in order for the left-right axis to form correctly. These activities can be seen as early as the 6-cell stage of the embryo however the exact time is unclear.[21][22]

Advantages/Disadvantages as a model system[edit]

C. elegans ortholog of Human Ataxin-2

Model organisms are used to study processes in growth, development, disease, and to better understand other organisms and their systems. C. elegans has advantages and disadvantages to being used as a model system depending on what is being studied.

One advantage of using C. elegans as a model system is the similarity between its molecular signaling and the signaling responsible for development control in humans. Many of C. elegans genes have been studied and manipulated making it useful as a prime model for human disease research. Benefits of C. elegans also include that the entire genome is sequenced and annotated, the availability of an RNAi library comprising approx. 80% of the genes in the genome, the ease of generating transgenic strains, and the recent development of gene-targeting approaches.[24] [25] By studying processes in the development of C. elegans and using them as a comparison model for human developmental processes, many questions have been answered regarding development in humans. These advantages range from simple knowledge about cellular structure to vaccine possibilities for neurodegenerative diseases. Lifespan has also been an element that has been studied in close relation between C. elegans and overall human development. Another benefit of using C. elegans as a model system would the speed at which they develop. C. elegans has a very short lifespan of 2-3 weeks, with a generation time of 3-4 days. This allows scientists to easily perform genetic studies and look at results from several generations in a matter of months.

While there are many advantages of using C. elegans as model organisms, the organism is not without disadvantages. Because the organism has a very simple body plan, its structure lacks many defined organs/tissues including a brain, blood, a defined fat cell, and internal organs.[26] The size of the C. elegans organism is also a disadvantage when being used in an experiment as a model organism. The organism’s small size leads to questions about whether or not the size would be appropriate for biochemistry experiments. Biochemistry covers so many aspects of these studies and it is important that those aspects are similar on both small and large scale. Because of this size difference, it has lead to a limited understanding of any tissue-specific signaling such as whether a gene is expressed in the hypodermis or the intestine.[26] Lab experiments with these simple organisms are also very limited due to lack of space and nutrients in cell cultures.

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  26. ^ a b Tissenbaum, Heidi A. (2015-01-30). "Using C. elegans for aging research". Invertebrate Reproduction & Development. 59 (sup1): 59–63. doi:10.1080/07924259.2014.940470. ISSN 0792-4259. PMC 4464094. PMID 26136622.{{cite journal}}: CS1 maint: PMC format (link)
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