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Developmental genetics of the Caenorhabditis elegans pharynx

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Marc Pilon

Published Online: May 23 2014

DOI: 10.1002/wdev.139

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The Caenorhabditis elegans pharynx is a rhythmically pumping organ composed initially of 80 cells that, through fusions, amount to 62 cells in the adult worm. During the first 100 min of development, most future pharyngeal cells are born and gather into a double‐plate primordium surrounded by a basal lamina. All pharyngeal cells express the transcription factor PHA‐4, of which the concentration increases throughout development, triggering a sequential activation of genes with promoters responding differentially to PHA‐4 protein levels. The oblong‐shaped pharyngeal primordium becomes polarized, many cells taking on wedge shapes with their narrow ends toward the center, hence forming an epithelial cyst. The primordium then elongates, and reorientations of the cells at the anterior and posterior ends form the mouth and pharyngeal‐intestinal openings, respectively. The 20 pharyngeal neurons establish complex but reproducible trajectories using ‘fishing line’ and growth cone‐driven mechanisms, and the gland cells also similarly develop their processes. The genetics behind many fate decisions and morphogenetic processes are being elucidated, and reveal the pharynx to be a fruitful model for developmental biologists. WIREs Dev Biol 2014, 3:263–280. doi: 10.1002/wdev.139 This article is categorized under: Gene Expression and Transcriptional Hierarchies > Cellular Differentiation Invertebrate Organogenesis > Worms Nervous System Development > Worms

Pharyngeal anatomy. The figure outlines the main features of the Caenorhabditis elegans pharynx of relevance for this review. (a) Outline of the pharynx in which the trajectories of the M1, M2L, and NSML neurons are drawn, together with M3R of which only the cell body is shown for clarity. Except for the unique M1, each of these cells has a similar contralateral cell with a mirror shape. The pale gray lines outline the boundaries between muscle cell layers: for example, the pm4 and pm5 muscle cells make up the bulk of the metacorpus and isthmus, respectively (two of each per sector). (b) A cross section in the isthmus, revealing the threefold symmetry with two sublateral sectors, and a dorsal sector, as well as the relative positions of the M1, M2, and NSM processes. Unlabelled ovals in the muscle folds of each sector represent other axons or gland cell ducts. The anatomy is from Albertson et al. and Axäng et al.

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Model for the development of the M2 axon. Elongation of the pm5 cells likely separates the cell bodies of the sister cells M2 and M3. However, M2 remains attached to M3, such that their separation causes lengthening of the M2 axon proximal trajectory through the isthmus (a, b). Later, the distal end of the M2 cell forms a growth cone that requires a signal from M3 to be specified correctly. M3 depends on its expression of mnm‐2 to produce this signal (c). The M2 growth cone then interprets local cues and establishes the two arcs of the distal end (d), and meets its contralateral cellular homolog at the midline where they become connected by a gap junction. Anterior is up. (Reprinted with permission from Ref . Copyright 2007 Elsevier Ltd.)

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Isthmus defect in pha‐2 mutants. In wild‐type worms (left), pm5 (green) and other isthmus cells elongate anteriorly while their nuclei remain in the nascent posterior bulb. This drives the formation of the narrowed, nucleus‐free isthmus. Near the time of hatching, two cells fuse in each muscle sector to create the multinucleated pm5 cells that make up the mature isthmus. In pha‐2 mutants (right), the pm5 cells have a weak cytoskeleton that does not drive anterior elongation nor prevent movement of nuclei into the isthmus, which therefore does not form. The result is that the metacorpus and posterior bulb remain near each other, connected by a short abnormally thick isthmus containing many nuclei. The state of cellular fusion in the pha‐2 mutant is not known.

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Cellular origins and positions of pharyngeal cells. Color‐coded fates of the pharyngeal cells in the 28‐cell embryo (a) and location of their nuclei in the mature pharynx (b). Note the approximate preservation of spatial relationships in the mature pharynx, and absence of nuclei in the isthmus. The lineage is from Sulston et al., and the anatomy is from Albertson et al.

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Overview of pharyngeal development. All pharyngeal cells are descendants of the ABa and MS cells which are born after 2 and 3 cell divisions of the zygote, respectively (a). ABa will produce 49 pharyngeal cells while MS will produce 39. These cells are born and migrate during gastrulation (b) to form two plates of cells 6–8 cells deep along the dorsal–ventral axis (c). Many cells then constrict along the midline facing apical surfaces to create an elongated epithelial cyst depicted as a cross section in (d). Reorientation of the cells at the anterior and posterior ends of the primordium create openings toward the mouth and intestine, and retraction of the apical tips of marginal cells create a lumen that runs through the entire pharynx as it elongates; thin cellular processes, such as the axons of the M2 and other neurons, are drawn by cellular elongations such as that of the pm5 muscle cells in the isthmus (e). Pharyngeal cells then complete their differentiation and morphogenesis, including completing growth cone‐driven axon trajectories, to produce a mature pharynx that will grow in size during larval development and of which the muscle cells will gradually become disorganized during aging (f). See text for details. The lineage is from Sulston et al., and the developmental processes shown are mostly from Portereiko and Mango, Rasmussen et al. and Rauthan et al.

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References

Albertson, DG, Thomson, JN. The pharynx of Caenorhabditis elegans. Philos Trans R Soc Lond B Biol Sci 1976, 275:299–325.
Sulston, JE, Schierenberg, E, White, JG, Thomson, JN. The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev Biol 1983, 100:64–119.
Avery, L, Shtonda, BB. Food transport in the C. elegans pharynx. J Exp Biol 2003, 206:2441–2457.
Raizen, DM, Avery, L. Electrical activity and behavior in the pharynx of Caenorhabditis elegans. Neuron 1994, 12:483–495.
Gaudet, J, Mango, SE. Regulation of organogenesis by the Caenorhabditis elegans FoxA Protein PHA‐4. Science 2002, 295:821–825.
Avery, L, You, YJ. C. elegans feeding. In: WormBook, ed. The C. elegans Research Community, WormBook. doi/10.1895/wormbook.1.150.1. Available at: http://www.wormbook.org. (Accessed May 21, 2012).
Mango, SE. The molecular basis of organ formation: insights from the C. elegans foregut. Annu Rev Cell Dev Biol 2009, 25:597–628.
Song, B‐M, Avery, L. The pharynx of the nematode C. elegans: a model system for the study of motor control. Worm 2013, 2:e21833.
Kormish, JD, Gaudet, J, McGhee, JD. Development of the C. elegans digestive tract. Curr Opin Genet Dev 2010, 20:346–354.
Altun, ZF, Herndon, LA, Crocker, C, Lints, R, Hall, DH. WormAtlas, 2014. Available at: http://www.wormatlas.org. (Accessed March 1, 2014).
Pilon, M. Fishing lines, time‐delayed guideposts, and other tricks used by developing pharyngeal neurons in Caenorhabditis elegans. Dev Dyn 2008, 237:2073–2080.
Heustis, RJ, Ng, HK, Brand, KJ, Rogers, MC, Le, LT, Specht, CA, Fuhrman, JA. Pharyngeal polysaccharide deacetylases affect development in the nematode C. elegans and deacetylate chitin in vitro. PLoS One 2012, 7:e40426.
Graham, PL, Johnson, JJ, Wang, S, Sibley, MH, Gupta, MC, Kramer, JM. Type IV collagen is detectable in most, but not all, basement membranes of Caenorhabditis elegans and assembles on tissues that do not express it. J Cell Biol 1997, 137:1171–1183.
Smit, RB, Schnabel, R, Gaudet, J. The HLH‐6 transcription factor regulates C. elegans pharyngeal gland development and function. PLoS Genet 2008, 4:e1000222.
Avery, L, Horvitzt, HR. Pharyngeal pumping continues after laser killing of the pharyngeal nervous system of C. elegans. Neuron 1989, 3:473–485.
Avery, L. Motor neuron M3 controls pharyngeal muscle relaxation timing in Caenorhabditis elegans. J Exp Biol 1993a, 175:283–297.
Wright, KA, Thomson, JN. The buccal capsule of C. elegans (Nematoda: Rhabditoidea): an ultrastructural study. Can J Zool 1981, 59:1952–1961.
Avery, L. The genetics of feeding in Caenorhabditis elegans. Genetics 1993b, 133:897–917.
Avery, L, Raizen, D, Lockery, S. Electrophysiological methods. Methods Cell Biol 1995, 48:251–269.
Mörck, C, Axäng, C, Pilon, M. A genetic analysis of axon guidance in the C. elegans pharynx. Dev Biol 2003, 260:158–175.
Rasmussen, JP, Reddy, SS, Priess, JR. Laminin is required to orient epithelial polarity in the C. elegans pharynx. Development 2012, 139:2050–2060.
Podbilewicz, B. Cell fusion. WormBook 2006:1–32.
Portereiko, MF, Mango, SE. Early morphogenesis of the Caenorhabditis elegans pharynx. Dev Biol 2001, 233:482–494.
Rauthan, M, Morck, C, Pilon, M. The C. elegans M3 neuron guides the growth cone of its sister cell M2 via the Kruppel‐like zinc finger protein MNM‐2. Dev Biol 2007, 311:185–199.
Goldstein, B, Hird, SN. Specification of the anteroposterior axis in Caenorhabditis elegans. Development 1996, 122:1467–1474.
Cheeks, RJ, Canman, JC, Gabriel, WN, Meyer, N, Strome, S, Goldstein, B. C. elegans PAR proteins function by mobilizing and stabilizing asymmetrically localized protein complexes. Curr Biol 2004, 14:851–862.
Duguay, D, Foty, RA, Steinberg, MS. Cadherin‐mediated cell adhesion and tissue segregation: qualitative and quantitative determinants. Dev Biol 2003, 253:309–323.
Leung, B, Hermann, GJ, Priess, JR. Organogenesis of the Caenorhabditis elegans intestine. Dev Biol 1999, 216:114–134.
Shaw, WR, Armisen, J, Lehrbach, NJ, Miska, EA. The conserved miR‐51 microRNA family is redundantly required for embryonic development and pharynx attachment in Caenorhabditis elegans. Genetics 2010, 185:897–905.
Bellocchio, EE, Reimer, RJ, Fremeau, RT Jr, Edwards, RH. Uptake of glutamate into synaptic vesicles by an inorganic phosphate transporter. Science 2000, 289:957–960.
Lee, RY, Sawin, ER, Chalfie, M, Horvitz, HR, Avery, L. EAT‐4, a homolog of a mammalian sodium‐dependent inorganic phosphate cotransporter, is necessary for glutamatergic neurotransmission in Caenorhabditis elegans. J Neurosci 1999, 19:159–167.
Starich, TA, Lee, RY, Panzarella, C, Avery, L, Shaw, JE. eat‐5 and unc‐7 represent a multigene family in Caenorhabditis elegans involved in cell‐cell coupling. J Cell Biol 1996, 134:537–548.
Jafari, G, Burghoorn, J, Kawano, T, Mathew, M, Mörck, C, Axäng, C, Ailion, M, Thomas, JH, Culotti, JG, Swoboda, P, et al. Genetics of extracellular matrix remodeling during organ growth using the Caenorhabditis elegans pharynx model. Genetics 2010, 186:969–982.
Mörck, C, Vivekanand, V, Jafari, G, Pilon, M. C. elegans ten‐1 is synthetic lethal with mutations in cytoskeleton regulators, and enhances many axon guidance defective mutants. BMC Dev Biol 2010, 10:55.
Schnabel, H, Schnabel, R. An organ‐specific differentiation Gene, pha‐1, from Caenorhabditis elegans. Science 1990, 250:686–688.
Benian, GM, Tinley, TL, Tang, X, Borodovsky, M. The Caenorhabditis elegans gene unc‐89, required fpr muscle M‐line assembly, encodes a giant modular protein composed of Ig and signal transduction domains. J Cell Biol 1996, 132:835–848.
Kalb, JM, Lau, KK, Goszczynski, B, Fukushige, T, Moons, D, Okkema, PG, McGhee, JD. pha‐4 is Ce‐fkh‐1, a fork head/HNF‐3α,β,γ homolog that functions in organogenesis of the C. elegans pharynx. Development 1998, 125:2171–2180.
Mango, SE, Lambie, EJ, Kimble, J. The pha‐4 gene is required to generate the pharyngeal primordium of Caenorhabditis elegans. Development 1994, 120:3019–3031.
Morck, C, Rauthan, M, Wagberg, F, Pilon, M. pha‐2 encodes the C. elegans ortholog of the homeodomain protein HEX and is required for the formation of the pharyngeal isthmus. Dev Biol 2004, 272:403–418.
Ao, W, Gaudet, J, Kent, WJ, Muttumu, S, Mango, SE. Environmentally induced foregut remodeling by PHA‐4/FoxA and DAF‐12/NHR. Science 2004, 305:1743–1746.
Gaudet, J, Muttumu, S, Horner, M, Mango, SE. Whole‐genome analysis of temporal gene expression during foregut development. PLoS Biol 2004, 2:e352.
Raharjo, WH, Logan, BC, Wen, S, Kalb, JM, Gaudet, J. In vitro and in vivo characterization of Caenorhabditis elegans PHA‐4/FoxA response elements. Dev Dyn 2010, 239:2219–2232.
Fakhouri, THI, Stevenson, J, Chisholm, AD, Mango, SE. Dynamic chromatin organization during foregut development mediated by the organ selector gene PHA‐4/FoxA. PLoS Genet 2010, 6:e1001060.
Labouesse, M, Mango, SE. Patterning the C. elegans embryo: moving beyond the cell lineage. Trends Genet 1999, 15:307–313.
Christensen, S, Kodoyianni, V, Bosenberg, M, Friedman, L, Kimble, J. lag‐1, a gene required for lin‐12 and glp‐1 signaling in Caenorhabditis elegans, is homologous to human CBF1 and Drosophila Su(H). Development 1996, 122:1373–1383.
Good, K, Ciosk, R, Nance, J, Neves, A, Hill, RJ, Priess, JR. The T‐box transcription factors TBX‐37 and TBX‐38 link GLP‐1/Notch signaling to mesoderm induction in C. elegans embryos. Development 2004, 131:1967–1978.
Smith, PA, Mango, SE. Role of T‐box gene tbx‐2 for anterior foregut muscle development in C. elegans. Dev Biol 2014, 196:211–223.
Neves, A, Priess, JR. The REF‐1 family of bHLH transcription factors pattern C. elegans embryos through Notch‐dependent and Notch‐independent pathways. Dev Cell 2005, 8:867–879.
Moskowitz, IP, Gendreau, SB, Rothman, JH. Combinatorial specification of blastomere identity by glp‐1‐dependent cellular interactions in the nematode Caenorhabditis elegans. Development 1994, 120:3325–3338.
Moskowitz, IP, Rothman, JH. lin‐12 and glp‐1 are required zygotically for early embryonic cellular interactions and are regulated by maternal GLP‐1 signaling in Caenorhabditis elegans. Development 1996, 122:4105–4117.
Broitman‐Maduro, G, Lin, KT‐H, Hung, WWK, Maduro, MF. Specification of the C. elegans MS blastomere by the T‐box factor TBX‐35. Development 2006, 133:3097–3106.
Marshall, SD, McGhee, JD. Coordination of ges‐1 expression between the Caenorhabditis pharynx and intestine. Dev Biol 2001, 239:350–363.
Zhong, M, Niu, W, Lu, ZJ, Sarov, M, Murray, JI, Janette, J, Raha, D, Sheaffer, KL, Lam, HYK, Preston, E, et al. Genome‐wide identification of binding sites defines distinct functions for Caenorhabditis elegans PHA‐4/FOXA in development and environmental response. PLoS Genet 2010, 6:e1000848.
Fay, DS, Qiu, X, Large, E, Smith, CP, Mango, S, Johanson, BL. The coordinate regulation of pharyngeal development in C. elegans by lin‐35/Rb, pha‐1, and ubc‐18. Dev Biol 2004, 271:11–25.
Granato, M, Schnabel, H, Schnabel, R. Genesis of an organ: molecular analysis of the pha‐1 gene. Development 1994, 120:3005–3017.
Mani, K, Fay, DS. A mechanistic basis for the coordinated regulation of pharyngeal morphogenesis in Caenorhabditis elegans by LIN‐35/Rb and UBC‐18‐ARI‐1. PLoS Genet 2009, 5:e1000510.
Polley, SRG, Kuzmanov, A, Kuang, J, Karpel, J, Lazetic, V, Karina, EI, Veo, BL, Fay, DS. Implicating SCF complexes in organogenesis in Caenorhabditis elegans. Genetics 2014, 196:211–223.
Fay, DS, Large, E, Han, M, Darland, M. lin‐35/Rb and ubc‐18, an E2 ubiquitin‐conjugating enzyme, function redundantly to control pharyngeal morphogenesis in C. elegans. Development 2003, 130:3319–3330.
Morck, C, Axang, C, Goksor, M, Pilon, M. Misexpression of acetylcholinesterases in the C. elegans pha‐2 mutant accompanies ultrastructural defects in pharyngeal muscle cells. Dev Biol 2006, 297:446–460.
Okkema, PG, Fire, A. The Caenorhabditis elegans NK‐2 class homeoprotein CEH‐22 is involved in combinatorial activation of gene expression in pharyngeal muscle. Development 1994, 120:2175–2186.
Haun, C, Alexander, J, Stainier, DY, Okkema, PG. Rescue of Caenorhabditis elegans pharyngeal development by a vertebrate heart specification gene. Proc Natl Acad Sci USA 1998, 95:5072–5075.
Okkema, PG, Ha, E, Haun, C, Chen, W, Fire, A. The Caenorhabditis elegans NK‐2 homeobox gene ceh‐22 activates pharyngeal muscle gene expression in combination with pha‐1 and is required for normal pharyngeal development. Development 1997, 124:3965–3973.
Lam, N, Chesney, MA, Kimble, J. Wnt signaling and CEH‐22/tinman/Nkx2.5 specify a stem cell niche in C. elegans. Curr Biol 2006, 16:287–295.
Chiang, JT, Steciuk, M, Shtonda, B, Avery, L. Evolution of pharyngeal behaviors and neuronal functions in free‐living soil nematodes. J Exp Biol 2006, 209:1859–1873.
Chilton, JK. Molecular mechanisms of axon guidance. Dev Biol 2006, 292:13–24.
Dickson, BJ. Molecular mechanisms of axon guidance. Science 2002, 298:1959–1964.
Tessier‐Lavigne, M, Goodman, CS. The molecular biology of axon guidance. Science 1996, 274:1123–1133.
Ogura, K, Wicky, C, Magnenat, L, Tobler, H, Mori, I, Muller, F, Ohshima, Y. Caenorhabditis elegans unc‐51 gene required for axonal elongation encodes a novel serine/threonine kinase. Genes Dev 1994, 8:2389–2400.
Okazaki, N, Yan, J, Yuasa, S, Ueno, T, Kominami, E, Masuho, Y, Koga, H, Muramatsu, M. Interaction of the Unc‐51‐like kinase and microtubule‐associated protein light chain 3 related proteins in the brain: possible role of vesicular transport in axonal elongation. Brain Res Mol Brain Res 2000, 85:1–12.
Steven, R, Kubiseski, TJ, Zheng, H, Kulkarni, S, Mancillas, J, Ruiz Morales, A, Hogue, CW, Pawson, T, Culotti, J. UNC‐73 activates the Rac GTPase and is required for cell and growth cone migrations in C. elegans. Cell 1998, 92:785–795.
Steven, R, Zhang, L, Culotti, J, Pawson, T. The UNC‐73/Trio RhoGEF‐2 domain is required in separate isoforms for the regulation of pharynx pumping and normal neurotransmission in C. elegans. Genes Dev 2005, 19:2016–2029.
Hedgecock, EM, Culotti, JG, Hall, DH. The unc‐5, unc‐6, and unc‐40 genes guide circumferential migrations of pioneer axons and mesodermal cells on the epidermis in C. elegans. Neuron 1990, 4:61–85.
Ishii, N, Wadsworth, WG, Stern, BD, Culotti, JG, Hedgecock, EM. UNC‐6, a laminin‐related protein, guides cell and pioneer axon migrations in C. elegans. Neuron 1992, 9:873–881.
Levy‐Strumpf, N, Culotti, JG. VAB‐8, UNC‐73 and MIG‐2 regulate axon polarity and cell migration functions of UNC‐40 in C. elegans. Nat Neurosci 2007, 10:161–168.
Quinn, CC, Pfeil, DS, Chen, E, Stovall, EL, Harden, MV, Gavin, MK, Forrester, WC, Ryder, EF, Soto, MC, Wadsworth, WG. UNC‐6/netrin and SLT‐1/slit guidance cues orient axon outgrowth mediated by MIG‐10/RIAM/lamellipodin. Curr Biol 2006, 16:845–853.
Watari‐Goshima, N, Ogura, K, Wolf, FW, Goshima, Y, Garriga, G. C. elegans VAB‐8 and UNC‐73 regulate the SAX‐3 receptor to direct cell and growth‐cone migrations. Nat Neurosci 2007, 10:169–176.
Hao, JC, Yu, TW, Fujisawa, K, Culotti, JG, Gengyo‐Ando, K, Mitani, S, Moulder, G, Barstead, R, Tessier‐Lavigne, M, Bargmann, CI. C. elegans slit acts in midline, dorsal‐ventral, and anterior‐posterior guidance via the SAX‐3/Robo receptor. Neuron 2001, 32:25–38.
Zallen, JA, Yi, BA, Bargmann, CI. The conserved immunoglobulin superfamily member SAX‐3/Robo directs multiple aspects of axon guidance in C. elegans. Cell 1998, 92:217–227.
Knobel, KM, Davis, WS, Jorgensen, EM, Bastiani, MJ. UNC‐119 suppresses axon branching in C. elegans. Development 2001, 128:4079–4092.
Maduro, M, Pilgrim, D. Identification and cloning of unc‐119, a gene expressed in the Caenorhabditis elegans nervous system. Genetics 1995, 141:977–988.
Much, JW, Slade, DJ, Klampert, K, Garriga, G, Wightman, B. The fax‐1 nuclear hormone receptor regulates axon pathfinding and neurotransmitter expression. Development 2000, 127:703–712.
Luo, S, Nonet, ML. Regulators of kinesin involved in polarized trafficking and axon outgrowth. J Biol 2006, 5:8.
Su, CW, Tharin, S, Jin, Y, Wightman, B, Spector, M, Meili, D, Tsung, N, Rhiner, C, Bourikas, D, Stoeckli, E, et al. The short coiled‐coil domain‐containing protein UNC‐69 cooperates with UNC‐76 to regulate axonal outgrowth and normal presynaptic organization in Caenorhabditis elegans. J Biol 2006, 5:9.
Gitai, Z, Yu, TW, Lundquist, EA, Tessier‐Lavigne, M, Bargmann, CI. The netrin receptor UNC‐40/DCC stimulates axon attraction and outgrowth through enabled and, in parallel, Rac and UNC‐115/AbLIM. Neuron 2003, 37:53–65.
Lundquist, EA, Herman, RK, Shaw, JE, Bargmann, CI. UNC‐115, a conserved protein with predicted LIM and actin‐binding domains, mediates axon guidance in C. elegans. Neuron 1998, 21:385–392.
Axäng, C, Rauthan, M, Hall, DH, Pilon, M. Developmental genetics of the C. elegans pharyngeal neurons NSML and NSMR. BMC Dev Biol 2008, 8:38.
George, SE, Simokat, K, Hardin, J, Chisholm, AD. The VAB‐1 Eph receptor tyrosine kinase functions in neural and epithelial morphogenesis in C. elegans. Cell 1998, 92:633–643.
Ghenea, S, Boudreau, JR, Lague, NP, Chin‐Sang, ID. The VAB‐1 Eph receptor tyrosine kinase and SAX‐3/Robo neuronal receptors function together during C. elegans embryonic morphogenesis. Development 2005, 132:3679–3690.
Refai, O, Rohs, P, Mains, PE, Gaudet, J. Extension of the Caenorhabditis elegans Pharyngeal M1 neuron axon is regulated by multiple mechanisms. G3 (Bethesda) 2013, 3:2015–2029.
Bray, D. Axonal growth in response to experimentally applied mechanical tension. Dev Biol 1984, 102:379–389.
Heiman, MG, Shaham, S. DEX‐1 and DYF‐7 establish sensory dendrite length by anchoring dendritic tips during cell migration. Cell 2009, 137:344–355.
Komuro, H, Yacubova, E. Recent advances in cerebellar granule cell migration. Cell Mol Life Sci 2003, 60:1084–1098.
Schmucker, D, Jackle, H, Gaul, U. Genetic analysis of the larval optic nerve projection in Drosophila. Development 1997, 124:937–948.
Bentley, D, Keshishian, H. Pathfinding by peripheral pioneer neurons in grasshoppers. Science 1982, 218:1082–1088.
Palka, J, Whitlock, KE, Murray, MA. Guidepost cells. Curr Opin Neurobiol 1992, 2:48–54.
Keleman, K, Ribeiro, C, Dickson, BJ. Comm function in commissural axon guidance: cell‐autonomous sorting of Robo in vivo. Nat Neurosci 2005, 8:156–163.
Kidd, T, Bland, KS, Goodman, CS. Slit is the midline repellent for the robo receptor in Drosophila. Cell 1999, 96:785–794.
Shen, K, Fetter, RD, Bargmann, CI. Synaptic specificity is generated by the synaptic guidepost protein SYG‐2 and its receptor, SYG‐1. Cell 2004, 116:869–881.
Horvitz, HR, Chalfie, M, Trent, C, Sulston, JE, Evans, PD. Serotonin and octopamine in the nematode Caenorhabditis elegans. Science 1982, 216:1012–1014.
Sze, JY, Victor, M, Loer, C, Shi, Y, Ruvkun, G. Food and metabolic signalling defects in a Caenorhabditis elegans serotonin‐synthesis mutant. Nature 2000, 403:560–564.
Nathoo, AN, Moeller, RA, Westlund, BA, Hart, AC. Identification of neuropeptide‐like protein gene families in Caenorhabditis elegans and other species. Proc Natl Acad Sci USA 2001, 98:14000–14005.
Sawin, ER, Ranganathan, R, Horvitz, HR. C. elegans locomotory rate is modulated by the environment through a dopaminergic pathway and by experience through a serotonergic pathway. Neuron 2000, 26:619–631.
Kamiguchi, H, Yoshihara, F. The role of endocytic l1 trafficking in polarized adhesion and migration of nerve growth cones. J Neurosci 2001, 21:9194–9203.
Ye, B, Zhang, Y, Song, W, Younger, SH, Jan, LY, Jan, YN. Growing dendrites and axons differ in their reliance on the secretory pathway. Cell 2007, 130:717–729.
Colavita, A, Culotti, JG. Suppressors of ectopic UNC‐5 growth cone steering identify eight genes involved in axon guidance in Caenorhabditis elegans. Dev Biol 1998, 194:72–85.
Forrester, WC, Garriga, G. Genes necessary for C. elegans cell and growth cone migrations. Development 1997, 124:1831–1843.
Zallen, JA, Kirch, SA, Bargmann, CI. Genes required for axon pathfinding and extension in the C. elegans nerve ring. Development 1999, 126:3679–3692.
Barriere, A, Felix, MA. High local genetic diversity and low outcrossing rate in Caenorhabditis elegans natural populations. Curr Biol 2005, 15:1176–1184.
Hall, DH, Hedgecock, EM. Kinesin‐related gene unc‐104 is required for axonal transport of synaptic vesicles in C. elegans. Cell 1991, 65:837–847.
Raharjo, WH, Ghai, V, Dineen, A, Bastiani, M, Gaudet, J. Cell architecture: surrounding muscle cells shape gland cell morphology in the Caenorhabditis elegans pharynx. Genetics 2011, 189:885–897.
Ghai, V, Gaudet, J. The CSL transcription factor LAG‐1 directly represses hlh‐6 expression in C. elegans. Dev Biol 2008, 322:334–344.
Ghai, V, Smit, RB, Gaudet, J. Transcriptional regulation of HLH‐6‐independent and subtype‐specific genes expressed in the Caenorhabditis elegans pharyngeal glands. Mech Dev 2012, 129:284–297.
Ferrier, A, Charron, A, Sadozai, Y, Switaj, L, Szutenbach, A, Smith, PA. Multiple phenotypes resulting from a mutagenesis screen for pharynx muscle mutations in Caenorhabditis elegans. PLoS One 2011, 6:e26594.
Norman, KR, Moerman, DG. α spectrin is essential for morphogenesis and body wall muscle formation in Caenorhabditis elegans. J Cell Biol 2002, 157:665–677.
McKeown, C, Praitis, V, Austin, J. sma‐1 encodes a βH‐spectrin homolog required for Caenorhabditis elegans morphogenesis. Development 1998, 125:2087–2098.
Straud, S, Lee, I, Song, B, Avery, L, You, Y‐j. The jaw of the worm: GTPase‐activating protein EAT‐17 regulates grinder formation in Caenorhabditis elegans. Genetics 2013, 195:115–125.
Avery, L, Horvitz, HR. A cell that dies during wild‐type C. elegans development can function as a neuron in a ced‐3 mutant. Cell 1987, 51:1071–1078.
Riddle, MR, Weintraub, A, Nguyen, KCQ, Hall, DH, Rothman, JH. Transdifferentiation and remodeling of post‐embryonic C. elegans cells by a single transcription factor. Development 2013, 140:4844–4849.
Axäng, C, Rauthan, M, Hall, DH, Pilon, M. The twisted pharynx phenotype in C. elegans. BMC Dev Biol 2007, 7:61.
Johnston, J, Iser, WB, Chow, DK, Goldberg, IG, Wolkow, CA. Quantitative image analysis reveals distinct structural transitions during aging in Caenorhabditis elegans tissues. PLoS One 2008, 3:e2821.
Shamir, L, Wolkow, CA, Goldberg, IG. Quantitative measurement of aging using image texture entropy. Bioinformatics 2009, 25:3060–3063.
Shen, EZ, Song, CQ, Lin, Y, Zhang, WH, Su, PF, Liu, WY, Zhang, P, Xu, J, Lin, N, Zhan, C, et al. Mitoflash frequency in early adulthood predicts lifespan in Caenorhabditis elegans. Nature 2014, 508:128–132.
Budovskaya, YV, Wu, K, Southworth, LK, Jiang, M, Tedesco, P, Johnson, TE, Kim, SK. An elt‐3/elt‐5/elt‐6 GATA transcription circuit guides aging in C. elegans. Cell 2008, 134:291–303.
Hardin, J. To thine own self be true: self‐fusion in single‐celled tubes. Dev Cell 2008, 14:465–466.
Laughlin, ST, Bertozzi, CR. In vivo imaging of Caenorhabditis elegans glycans. ACS Chem Biol 2009, 4:1068–1072.
Keskiaho, K, Kukkola, L, Page, AP, Winter, AD, Vuoristo, J, Sormunen, R, Nissi, R, Riihimaa, P, Myllyharju, J. Characterization of a novel Caenorhabditis elegans prolyl 4‐hydroxylase with a unique substrate specificity and restricted expression in the pharynx and excretory duct. J Biol Chem 2008, 283:10679–10689.
Wadsworth, WG, Bhatt, H, Hedgecock, EM. Neuroglia and pioneer neurons express UNC‐6 to provide global and local netrin cues for guiding migrations in C. elegans. Neuron 1996, 16:35–46.
Colavita, A, Krishna, S, Zheng, H, Padgett, RW, Culotti, JG. Pioneer axon guidance by UNC‐129, a C. elegans TGF‐β. Science 1998, 281:706–709.

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