Editing Caenorhabditis elegans (section)

==Development==
[[File:C._elegans_embryo_development.tif|thumb|right|''C. elegans'' embryonic development]]

=== Embryonic development ===
The fertilized zygote undergoes rotational holoblastic [[Cleavage (embryo)|cleavage]].

Sperm entry into the oocyte commences formation of an anterior-posterior axis.<ref name="pmid8625834">{{cite journal | vauthors = Goldstein B, Hird SN | title = Specification of the anteroposterior axis in Caenorhabditis elegans | journal = Development | volume = 122 | issue = 5 | pages = 1467–74 | date = May 1996 | pmid = 8625834 | doi = 10.1242/dev.122.5.1467 | url = https://pubmed.ncbi.nlm.nih.gov/8625834/ }}</ref> The sperm [[microtubule organizing center]] directs the movement of the sperm [[pronucleus]] to the future posterior pole of the embryo, while also inciting the movement of [[Cell polarity|PAR proteins]], a group of cytoplasmic determination factors, to their proper respective locations.<ref>{{cite book | title=Developmental biology| edition=11th| author=Gilbert SF| year=2016| pages=268| publisher=Sinauer| isbn=9781605354705}}</ref> As a result of the difference in PAR protein distribution, the first cell division is highly [[asymmetric cell division|asymmetric]].<ref name="pmid7758115">{{cite journal | vauthors = Guo S, Kemphues KJ | title = par-1, a gene required for establishing polarity in ''C. elegans'' embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed | journal = Cell | volume = 81 | issue = 4 | pages = 611–20 | date = May 1995 | pmid = 7758115 | doi = 10.1016/0092-8674(95)90082-9 | doi-access = free }}</ref> ''C. elegans'' [[embryogenesis]] is among the best understood examples of asymmetric cell division.<ref name="ReferenceA">{{cite journal | vauthors = Gönczy P, Rose LS | title = Asymmetric cell division and axis formation in the embryo | journal = WormBook | pages = 1–20 | date = October 2005 | pmid = 18050411 | pmc = 4780927 | doi = 10.1895/wormbook.1.30.1 }}</ref>

All cells of the [[germline]] arise from a single [[primordial germ cell]], called the ''P4'' cell, established early in [[embryogenesis]].<ref>Kimble J, Crittenden SL. Germline proliferation and its control. 2005 Aug 15. In: WormBook: The Online Review of C. elegans Biology [Internet]. Pasadena (CA): WormBook; 2005-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK19769/</ref><ref name="wormbase0006773">{{cite encyclopedia | title=WBbt:0006773 (anatomy term) | encyclopedia=[[WormBase]] |edition=WS242 |id=WBbt:0006773 |date=May 14, 2014}}</ref> This primordial cell divides to generate two germline precursors that do not divide further until after hatching.<ref name="wormbase0006773"/>

==== Axis formation ====
The resulting daughter cells of the first cell division are called the AB cell (containing PAR-6 and PAR-3) and the P1 cell (containing PAR-1 and PAR-2). A second cell division produces the ABp and ABa cells from the AB cell, and the EMS and P2 cells from the P1 cell. This division establishes the dorsal-ventral axis, with the ABp cell forming the dorsal side and the EMS cell marking the ventral side.<ref>{{cite book | title=Developmental biology| edition=11th| author=Gilbert SF| year=2016| pages=272| publisher=Sinauer| isbn=9781605354705}}</ref> Through [[Wnt signaling pathway|Wnt signaling]], the P2 cell instructs the EMS cell to divide along the anterior-posterior axis.<ref name="pmid9288749">{{cite journal | vauthors = Thorpe CJ, Schlesinger A, Carter JC, Bowerman B | title = Wnt signaling polarizes an early ''C. elegans'' blastomere to distinguish endoderm from mesoderm | journal = Cell | volume = 90 | issue = 4 | pages = 695–705 | date = August 1997 | pmid = 9288749 | doi = 10.1016/s0092-8674(00)80530-9 | doi-access = free }}</ref> Through [[Notch signaling pathway|Notch signaling]], the P2 cell differentially specifies the ABp and ABa cells, which further defines the dorsal-ventral axis. The left-right axis also becomes apparent early in embryogenesis, although it is unclear exactly when specifically the axis is determined. However, most theories of the L-R axis development involve some kind of differences in cells derived from the AB cell.<ref>{{cite journal | vauthors = Pohl C, Bao Z | title = Chiral forces organize left-right patterning in ''C. elegans'' by uncoupling midline and anteroposterior axis | journal = Developmental Cell | volume = 19 | issue = 3 | pages = 402–12 | date = September 2010 | pmid = 20833362 | pmc = 2952354 | doi = 10.1016/j.devcel.2010.08.014 }} {{cite journal | pmid = 3073266 | volume=16 | title=[Quantification of sebaceous excretion in volunteers: influence of chronological age, sex and race] | year=1988 | journal=Med Cutan Ibero Lat Am | pages=439–44 | vauthors=Villares JC, Carlini EA| issue=6 }} {{cite book | title=Developmental biology| edition=11th| author=Gilbert SF| year=2016| pages=269| publisher=Sinauer| isbn=9781605354705}}</ref>

==== Gastrulation ====
Gastrulation occurs after the embryo reaches the 24-cell stage.<ref name="pmid1601187">{{cite journal | vauthors = Skiba F, Schierenberg E | title = Cell lineages, developmental timing, and spatial pattern formation in embryos of free-living soil nematodes | journal = Developmental Biology | volume = 151 | issue = 2 | pages = 597–610 | date = June 1992 | pmid = 1601187 | doi = 10.1016/0012-1606(92)90197-o | url = https://pubmed.ncbi.nlm.nih.gov/1601187 }}</ref> ''C. elegans'' are a species of [[protostome]]s, so the blastopore eventually forms the mouth. Involution into the blastopore begins with movement of the [[endoderm]] cells and subsequent formation of the gut, followed by the P4 germline precursor, and finally the [[mesoderm]] cells, including the cells that eventually form the pharynx. Gastrulation ends when [[epiboly]] of the hypoblasts closes the blastopore.<ref>{{cite book | title=Developmental biology| edition=11th| author=Gilbert SF| year=2016| pages=273| publisher=Sinauer| isbn=9781605354705}}</ref>

=== Post-embryonic development ===
[[File:C_elegans_developmental_stages.svg|thumb|300px|right|   Anatomy and scale of ''C. elegans'' developmental stages]]
[[File:C_elegans_life_cycle.svg|thumb|300px|right|   Life cycle and developmental stages of ''C. elegans'']]

Under environmental conditions favourable for [[reproduction]], hatched [[larvae]] develop through four larval stages - L1, L2, L3, and L4 - in just 3 days at 20&nbsp;°C. When conditions are stressed, as in food insufficiency, excessive population density or high temperature, ''C. elegans'' can enter an alternative third larval stage, L2d, called the [[dauer larva|dauer]] stage (''Dauer'' is German for permanent). A specific dauer pheromone regulates entry into the dauer state. This pheromone is composed of similar derivatives of the 3,6-dideoxy sugar, [[ascarylose]]. Ascarosides, named after the ascarylose base, are involved in many sex-specific and social behaviors.<ref>{{Cite journal|last1=Ludewig|first1=Andreas H.|last2=Schroeder|first2=Frank C.|date=2013-01-18|title=Ascaroside signaling in C. elegans|journal=WormBook|pages=1–22|doi=10.1895/wormbook.1.155.1|issn=1551-8507|pmc=3758900|pmid=23355522}}</ref> In this way, they constitute a chemical language that ''C. elegans'' uses to modulate various phenotypes. Dauer larvae are stress-resistant; they are thin and their mouths are sealed with a characteristic dauer cuticle and cannot take in food. They can remain in this stage for a few months.<ref name="Introduction to C. Elegans">{{cite web |title=Introduction to ''C. Elegans'' |url=http://avery.rutgers.edu/WSSP/StudentScholars/project/introduction/worms.html |work=C. Elegans as a model organism |publisher=Rutgers University |url-status=dead |archive-url=https://web.archive.org/web/20020818213550/http://avery.rutgers.edu/WSSP/StudentScholars/project/introduction/worms.html |archive-date=2002-08-18 |access-date=August 15, 2014}}</ref><ref>{{Cite web|url=http://www.wormatlas.org/hermaphrodite/introduction/mainframe.htm|title = Handbook - Introduction}}</ref> The stage ends when conditions improve favour further growth of the larva, now moulting into the L4 stage, even though the gonad development is arrested at the L2 stage.<ref>{{Cite web|url=http://www.wormbook.org/chapters/www_dauer/dauer.html|title=Dauer|website=www.wormbook.org|access-date=2018-09-27}}</ref>

Each stage transition is punctuated by a molt of the worm's transparent cuticle. Transitions through these stages are controlled by genes of the heterochronic pathway, an evolutionarily conserved set of regulatory factors.<ref name="pmid20232378">{{cite journal | vauthors = Resnick TD, McCulloch KA, Rougvie AE | title = miRNAs give worms the time of their lives: small RNAs and temporal control in ''Caenorhabditis elegans'' | journal = Developmental Dynamics | volume = 239 | issue = 5 | pages = 1477–89 | date = May 2010 | pmid = 20232378 | pmc = 4698981 | doi = 10.1002/dvdy.22260 }}</ref> Many heterochronic genes code for [[microRNA]]s, which repress the expression of heterochronic [[transcription factor]]s and other heterochronic miRNAs.<ref name="pmid23962842">{{Cite book | vauthors = Rougvie AE, Moss EG | title = Developmental transitions in ''C. elegans'' larval stages | chapter = Developmental Transitions in C. Elegans Larval Stages | journal = Current Topics in Developmental Biology | series = Developmental Timing | volume = 105 | pages = 153–80 | year = 2013 | publisher = Academic Press | pmid = 23962842 | doi = 10.1016/B978-0-12-396968-2.00006-3 | url = https://pubmed.ncbi.nlm.nih.gov/23962842 | isbn = 9780123969682 }}</ref> miRNAs were originally discovered in ''C. elegans.''<ref name="pmid8252621">{{cite journal | vauthors = Lee RC, Feinbaum RL, Ambros V | title = The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 | journal = Cell | volume = 75 | issue = 5 | pages = 843–54 | date = December 1993 | pmid = 8252621 | doi = 10.1016/0092-8674(93)90529-y | doi-access = free }}</ref> Important developmental events controlled by heterochronic genes include the division and eventual [[syncytium|syncitial]] fusion of the hypodermic seam cells, and their subsequent secretion of the alae in young adults. It is believed that the heterochronic pathway represents an evolutionarily conserved predecessor to [[circadian rhythm|circadian clocks]].<ref name="pmid15691769">{{cite journal | vauthors = Banerjee D, Kwok A, Lin SY, Slack FJ | title = Developmental timing in ''C. elegans'' is regulated by kin-20 and tim-1, homologs of core circadian clock genes | journal = Developmental Cell | volume = 8 | issue = 2 | pages = 287–95 | date = February 2005 | pmid = 15691769 | doi = 10.1016/j.devcel.2004.12.006 | doi-access = free }}</ref>

Some nematodes have a fixed, genetically determined number of cells, a phenomenon known as [[eutely]]. The adult ''C. elegans'' hermaphrodite has 959 somatic cells and the male has 1033 cells,<ref>{{Cite journal|last1=Sulston|first1=J.E.|last2=Horvitz|first2=H.R.|date=March 1977|title=Post-embryonic cell lineages of the nematode, Caenorhabditis elegans|url=https://linkinghub.elsevier.com/retrieve/pii/0012160677901580|journal=Developmental Biology|language=en|volume=56|issue=1|pages=110–156|doi=10.1016/0012-1606(77)90158-0|pmid=838129}}</ref><ref>{{Cite journal|last1=Sulston|first1=J.E.|last2=Schierenberg|first2=E.|last3=White|first3=J.G.|last4=Thomson|first4=J.N.|date=November 1983|title=The embryonic cell lineage of the nematode Caenorhabditis elegans|url=https://linkinghub.elsevier.com/retrieve/pii/0012160683902014|journal=Developmental Biology|language=en|volume=100|issue=1|pages=64–119|doi=10.1016/0012-1606(83)90201-4|pmid=6684600}}</ref><ref name="Sammut 385–390">{{Cite journal|last1=Sammut|first1=Michele|last2=Cook|first2=Steven J.|last3=Nguyen|first3=Ken C. Q.|last4=Felton|first4=Terry|last5=Hall|first5=David H.|last6=Emmons|first6=Scott W.|last7=Poole|first7=Richard J.|last8=Barrios|first8=Arantza|date=October 2015|title=Glia-derived neurons are required for sex-specific learning in C. elegans|journal=Nature|language=en|volume=526|issue=7573|pages=385–390|doi=10.1038/nature15700|issn=0028-0836|pmc=4650210|pmid=26469050|bibcode=2015Natur.526..385S}}</ref> although it has been suggested that the number of their intestinal cells can increase by one to three in response to gut microbes experienced by mothers.<ref>{{Cite journal|last1=Ohno|first1=Hayao|last2=Bao|first2=Zhirong|date=2020-11-14|title=Small RNAs couple embryonic developmental programs to gut microbes|journal=bioRxiv|url=http://biorxiv.org/lookup/doi/10.1101/2020.11.13.381830|language=en|doi=10.1101/2020.11.13.381830|s2cid=227060212}}</ref> Much of the literature describes the cell number in males as 1031, but the discovery of a pair of left and right MCM neurons increased the number by two in 2015.<ref name="Sammut 385–390"/>  The number of cells does not change after cell division ceases at the end of the larval period, and subsequent growth is due solely to an increase in the size of individual cells.<ref>{{cite book |title=Invertebrate Zoology |edition=7th |last1=Ruppert |first1=Edward E. |last2=Fox | first2=Richard S. |last3=Barnes |first3=Robert D. | name-list-style = vanc |year=2004 |publisher=Cengage Learning |isbn=978-81-315-0104-7 |page=753 }}</ref>