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Coordinating signaling pathways between cell types to control anterior morphogenesis in C. elegans


Coordinating signaling pathways between cell types to control anterior morphogenesis in C. elegans

Richard, Victoria (2021) Coordinating signaling pathways between cell types to control anterior morphogenesis in C. elegans. Masters thesis, Concordia University.

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Morphogenesis is crucial for the development of tissues which must be coordinated to give rise to complex structures in the context of an organism. Mechanisms at the single cell, tissue and multi-tissue levels contribute to the complexities in studying morphogenesis. In C. elegans, prior studies uncovered mechanisms regulating epidermal and pharyngeal morphogenesis, but how these and other tissues are coordinated to give rise to the anterior lumen remained a black box. We characterized anterior morphogenesis to determine how the epidermal, pharyngeal and neuroblast (neuronal precursor) cells move and are positioned relative to one another, and to identify signaling events that regulate their coordination. We found that the first visible marker of the future anterior lumen are projections from the anterior-most pharyngeal cells (arcade cells) which form a stable rosette and express the polarity protein PAR-6. These projections are surrounded by subsets of polarized neuroblasts with PAR-6-enriched projections that organize into patterns forming two pentagons and a semi-circle. The anterior epidermal cells migrate toward the projections and ultimately join with the pharyngeal cells for their successful epithelialization. We found that the ventral epidermal cells migrate using F-actin-rich projections which come close to, but do not cross the semi-circle of foci suggesting that the cells corresponding to these foci provide guidance cues. Blocking neuroblast cell division and disrupting the patterns of polarized neuroblasts caused a decrease in the number of epidermal F-actin projections and delayed their migration. We propose that signals associated with the neuronal and/or glial cells control anterior epidermal cell migration. To identify these signals, we performed RNAi to several guidance cues and their receptors, and found that slit (slt-1) and sax/robo (sax-3) are required for neuroblast positioning and epidermal cell migration. This work provides new insights on the mechanisms underlying the multi-tissue cooperation required for successful anterior morphogenesis of C. elegans embryos.

Divisions:Concordia University > Faculty of Arts and Science > Biology
Item Type:Thesis (Masters)
Authors:Richard, Victoria
Institution:Concordia University
Degree Name:M. Sc.
Date:9 August 2021
Thesis Supervisor(s):Piekny, Alisa
Keywords:C. elegans; Morphogenesis; Rosettes; Polarity; Cell migration; Contractility; Adhesion
ID Code:988908
Deposited On:29 Nov 2021 16:58
Last Modified:29 Nov 2021 16:58


Ackley, B. D. (2014). Wnt-signaling and planar cell polarity genes regulate axon guidance along the anteroposterior axis in C. elegans. Developmental Neurobiology, 74(8), 781–796. https://doi.org/10.1002/dneu.22146
Ahnn, J., & Fire, A. (1994). A screen for genetic loci required for body-wall muscle development during embryogenesis in Caenorhabditis elegans. Genetics, 137(2), 483–498. https://doi.org/10.1093/genetics/137.2.483
Barnes, K. M., Fan, L., Moyle, M. W., Brittin, C. A., Xu, Y., Colón-Ramos, D. A., Santella, A., & Bao, Z. (2020). Cadherin preserves cohesion across involuting tissues during C. Elegans neurulation. ELife, 9, 1–19. https://doi.org/10.7554/eLife.58626
Beatty, A., Morton, D., & Kemphues, K. (2010). The C. elegans homolog of Drosophila Lethal giant larvae functions redundantly with PAR-2 to maintain polarity in the early embryo. Development (Cambridge, England), 137(23), 3995–4004. https://doi.org/10.1242/DEV.056028
Bernadskaya, Y. Y., Wallace, A., Nguyen, J., Mohler, W. A., & Soto, M. C. (2012). UNC-40/DCC, SAX-3/Robo, and VAB-1/Eph Polarize F-Actin during Embryonic Morphogenesis by Regulating the WAVE/SCAR Actin Nucleation Complex. PLoS Genetics, 8(8). https://doi.org/10.1371/journal.pgen.1002863
Bilder, D., Schober, M., & Perrimon, N. (2003). Integrated activity of PDZ protein complexes regulates epithelial polarity. Nature Cell Biology 5. https://doi.org/10.1038/ncb897
Blankenship, J. T., Backovic, S. T., Sanny, J. S. S. P., Weitz, O., & Zallen, J. A. (2006). Multicellular Rosette Formation Links Planar Cell Polarity to Tissue Morphogenesis. Developmental Cell, 11(4), 459–470. https://doi.org/10.1016/j.devcel.2006.09.007
Brenner, S. (1974). The genetics of Caenorhabditis elegans. Genetics, 77(1), 71–94. https://doi.org/10.1093/genetics/77.1.71
Brose, K., Bland, K., Wang, K., Arnott, D., Henzel, W., Goodman, C., Tessier-Lavigne, M., & Kidd, T. (1999). Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance. Cell, 96(6), 795–806. https://doi.org/10.1016/S0092-8674(00)80590-5
Chanal, P., & Labouesse, M. (1997). A screen for genetic loci required for hypodermal cell and glial-like cell development during Caenorhabditis elegans embryogenesis. Genetics, 146(1), 207–226. /pmc/articles/PMC1207936/?report=abstract
Chin-Sang, I. D., George, S. E., Ding, M., Moseley, S. L., Lynch, A. S., & Chisholm, A. D. (1999). The ephrin VAB-2/EFN-1 functions in neuronal signaling to regulate epidermal morphogenesis in C. elegans. Cell, 99(7), 781–790. https://doi.org/10.1016/S0092-8674(00)81675-X
Chisholm, A. D., & Hardin, J. (2005). Epidermal morphogenesis. WormBook : The Online Review of C. Elegans Biology, 1–22. https://doi.org/10.1895/wormbook.1.35.1
Clainche, C. Le, & Carlier, M.-F. (2008). Regulation of Actin Assembly Associated With Protrusion and Adhesion in Cell Migration. Physiological Reviews, 88(2), 489–513. https://doi.org/10.1152/PHYSREV.00021.2007
Costa, M., Raich, W., Agbunag, C., B, L., Hardin, J., & Priess, J. R. (1998). A putative catenin-cadherin system mediates morphogenesis of the Caenorhabditis elegans embryo. The Journal of Cell Biology, 141(1), 297–308. https://doi.org/10.1083/JCB.141.1.297
Drubin, D. G., & Nelson, W. J. (1996). Origins of Cell Polarity Review. In Cell (Vol. 84).
Fan, L., Kovacevic, I., Heiman, M. G., & Bao, Z. (2019). A multicellular rosette-mediated collective dendrite extension. ELife, 8. https://doi.org/10.7554/eLife.38065
Fotopoulos, N., Wernike, D., Chen, Y., Makil, N., Marte, A., & Piekny, A. (2013). Caenorhabditis elegans anillin (ani-1) regulates neuroblast cytokinesis and epidermal morphogenesis during embryonic development. Developmental Biology, 383(1), 61–74. https://doi.org/10.1016/j.ydbio.2013.08.024
Gettner, S. N., Kenyon, C., & Reichardt, L. F. (1995). Characterization of βpat-3 heterodimers, a family of essential integrin receptors in C. elegans. Journal of Cell Biology, 129(4), 1127–1141. https://doi.org/10.1083/jcb.129.4.1127
Ghenea, S., Boudreau, J. R., Lague, N. P., & Chin-Sang, I. D. (2005). The VAB-1 Eph receptor tyrosine kinase and SAX-3/Robo neuronal receptors function together during C. elegans embryonic morphogenesis. Development, 132(16), 3679–3690. https://doi.org/10.1242/dev.01947
Goley, E. D., & Welch, M. D. (2006). The ARP2/3 complex: An actin nucleator comes of age. In Nature Reviews Molecular Cell Biology (Vol. 7, Issue 10, pp. 713–726). https://doi.org/10.1038/nrm2026
Grimbert, S., Mastronardi, K., Richard, V., Christensen, R., Law, C., Zardoui, K., Fay, D., & Piekny, A. (2021). Multi-tissue patterning drives anterior morphogenesis of the C. elegans embryo. Developmental Biology, 471, 49–64. https://doi.org/10.1016/j.ydbio.2020.12.003
Harding, M. J., McGraw, H. F., & Nechiporuk, A. (2014). The roles and regulation of multicellular rosette structures during morphogenesis. Development (Cambridge), 141(13), 2549–2558. https://doi.org/10.1242/dev.101444
Hoege, C., & Hyman, A. A. (2013). Principles of PAR polarity in Caenorhabditis elegans embryos. In Nature Reviews Molecular Cell Biology (Vol. 14, Issue 5, pp. 315–322). https://doi.org/10.1038/nrm3558
Ikegami, R., Simokat, K., Zheng, H., Brown, L., Garriga, G., Hardin, J., & Culotti, J. (2012). Semaphorin and Eph receptor signaling guide a series of cell movements for ventral enclosure in C. elegans. Current Biology, 22(1), 1–11. https://doi.org/10.1016/j.cub.2011.12.009
Kamath, R. S., Martinez-Campos, M., Zipperlen, P., Fraser, A. G., & Ahringer, J. (2001). Effectiveness of specific RNA-mediated interference through ingested double-stranded RNA in Caenorhabditis elegans. Genome Biology, 2(1). https://doi.org/10.1186/gb-2000-2-1-research0002
Korswagen, H. C. (2002). Canonical and non-canonical Wnt signaling pathways in Caenorhabditis elegans: variations on a common signaling theme. BioEssays, 24(9), 801–810. https://doi.org/10.1002/BIES.10145
Kuzmanov, A., Yochem, J., & Fay, D. S. (2014). Analysis of PHA-1 reveals a limited role in pharyngeal development and novel functions in other tissues. Genetics, 198(1), 259–268. https://doi.org/10.1534/genetics.114.166876
Labouesse, M. (2006). Epithelial junctions and attachments. WormBook : The Online Review of C. Elegans Biology, 1–21. https://doi.org/10.1895/wormbook.1.56.1
Lecroisey, C., Ségalat, L., & Gieseler, K. (2007). The C. elegans dense body: Anchoring and signaling structure of the muscle. In Journal of Muscle Research and Cell Motility (Vol. 28, Issue 1, pp. 79–87). Springer Netherlands. https://doi.org/10.1007/s10974-007-9104-y
Low, I. I. C., Williams, C. R., Chong, M. K., McLachlan, I. G., Wierbowski, B. M., Kolotuev, I., & Heiman, M. G. (2019). Morphogenesis of neurons and glia within an epithelium. Development (Cambridge), 146(4). https://doi.org/10.1242/dev.171124
Mango, S. E. (2007). The C. elegans pharynx: a model for organogenesis. WormBook : The Online Review of C. Elegans Biology, 1–26. https://doi.org/10.1895/wormbook.1.129.1
Mango, S. E., Lambie, E. J., & Kimble, J. (1994). The pha-4 gene is required to generate the pharyngeal primordium of Caenorhabditis elegans. Development, 120(10), 3019–3031. https://doi.org/10.1242/dev.120.10.3019
Martin, A. C., & Goldstein, B. (2014). Apical constriction: Themes and variations on a cellular mechanism driving morphogenesis. In Development (Cambridge) (Vol. 141, Issue 10, pp. 1987–1998). Company of Biologists Ltd. https://doi.org/10.1242/dev.102228
Mentink, R. A., Middelkoop, T. C., Rella, L., Ji, N., Tang, C. Y., Betist, M. C., vanOudenaarden, A., & Korswagen, H. C. (2014). Cell intrinsic modulation of wnt signaling controls neuroblast migration in c.elegans. Developmental Cell, 31(2), 188–201. https://doi.org/10.1016/j.devcel.2014.08.008
Motegi, F., & Sugimoto, A. (2006). Sequential functioning of the ECT-2 RhoGEF, RHO-1 and CDC-42 establishes cell polarity in Caenorhabditis elegans embryos. Nature Cell Biology 2006 8:9, 8(9), 978–985. https://doi.org/10.1038/ncb1459
Munro, E., Nance, J., & Priess, J. R. (2004). Cortical Flows Powered by Asymmetrical Contraction Transport PAR Proteins to Establish and Maintain Anterior-Posterior Polarity in the Early C. elegans Embryo. Developmental Cell, 7(3), 413–424. https://doi.org/10.1016/J.DEVCEL.2004.08.001
Nobes, C. D., & Hall, A. (1995). Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell, 81(1), 53–62. https://doi.org/10.1016/0092-8674(95)90370-4
Ouellette, M. H., Martin, E., Lacoste-Caron, G., Hamiche, K., & Jenna, S. (2016). Spatial control of active CDC-42 during collective migration of hypodermal cells in Caenorhabditis elegans. Journal of Molecular Cell Biology, 8(4), 313–327. https://doi.org/10.1093/jmcb/mjv062
Patel, F. B., Bernadskaya, Y. Y., Chen, E., Jobanputra, A., Pooladi, Z., Freeman, K. L., Gally, C., Mohler, W. A., & Soto, M. C. (2008). The WAVE/SCAR complex promotes polarized cell movements and actin enrichment in epithelia during C. elegans embryogenesis. Developmental Biology, 324(2), 297–309. https://doi.org/10.1016/j.ydbio.2008.09.023
Portereiko, M. F., & Mango, S. E. (2001). Early morphogenesis of the Caenorhabditis elegans pharynx. Developmental Biology, 233(2), 482–494. https://doi.org/10.1006/dbio.2001.0235
Portereiko, M. F., Saam, J., & Mango, S. E. (2004). ZEN-4/MKLP1 is required to polarize the foregut epithelium. Current Biology, 14(11), 932–941. https://doi.org/10.1016/j.cub.2004.05.052
Raich, W. B., Agbunag, C., & Hardin, J. (1999). Rapid epithelial-sheet sealing in the Caenorhabditis elegans embryo requires cadherin-dependent filopodial priming. Current Biology, 9(20), 1139–1146. https://doi.org/10.1016/S0960-9822(00)80015-9
Rapti, G., Li, C., Shan, A., Lu, Y., & Shaham, S. (2017). Glia initiate brain assembly through noncanonical Chimaerin-Furin axon guidance in C. elegans. Nature Neuroscience, 20(10), 1350–1360. https://doi.org/10.1038/nn.4630
Rasmussen, J. P., Reddy, S. S., & Priess, J. R. (2012). Laminin is required to orient epithelial polarity in the C. elegans pharynx. Development, 139(11), 2050–2060. https://doi.org/10.1242/dev.078360
Ridley, A. J., Schwartz, M. A., Burridge, K., Firtel, R. A., Ginsberg, M. H., Borisy, G., Parsons, J. T., & Horwitz, A. R. (2003). Cell Migration: Integrating Signals from Front to Back. In Science (Vol. 302, Issue 5651, pp. 1704–1709). American Association for the Advancement of Science. https://doi.org/10.1126/science.1092053
Rodriguez-Boulan, E., & Macara, I. G. (2014). Organization and execution of the epithelial polarity programme. Nature Reviews Molecular Cell Biology 2014 15:4, 15(4), 225–242. https://doi.org/10.1038/nrm3775
Rodriguez-Diaz, A., Toyama, Y., Abravanel, D. L., Wiemann, J. M., Wells, A. R., Tulu, U. S., Edwards, G. S., & Kiehart, D. P. (2008). Actomyosin purse strings: renewable resources that make morphogenesis robust and resilient. HFSP Journal, 2(4), 220. https://doi.org/10.2976/1.2955565
Rørth, P. (2009). Collective cell migration. Annual Review of Cell and Developmental Biology, 25, 407–429. https://doi.org/10.1146/annurev.cellbio.042308.113231
Shah, P. K., Tanner, M. R., Kovacevic, I., Rankin, A., Marshall, T. E., Noblett, N., Tran, N. N., Roenspies, T., Hung, J., Chen, Z., Slatculescu, C., Perkins, T. J., Bao, Z., & Colavita, A. (2017). PCP and SAX-3/Robo Pathways Cooperate to Regulate Convergent Extension-Based Nerve Cord Assembly in C. elegans. Developmental Cell, 41(2), 195-203.e3. https://doi.org/10.1016/j.devcel.2017.03.024
Sharma, M., Castro-Piedras, I., Simmons, G. E., Jr, & Pruitt, K. (2018). Dishevelled: a masterful conductor of complex Wnt signals. Cellular Signalling, 47, 52. https://doi.org/10.1016/J.CELLSIG.2018.03.004
Skiba, F., & Schierenberg, E. (1992). Cell lineages, developmental timing, and spatial pattern formation in embryos of free-living soil nematodes. Developmental Biology, 151(2), 597–610. https://doi.org/10.1016/0012-1606(92)90197-O
Song, S., Zhang, B., Sun, H., Li, X., Xiang, Y., Liu, Z., Huang, X., & Ding, M. (2010). A wnt-frz/ror-dsh pathway regulates neurite outgrowth in caenorhabditis elegans. PLoS Genetics, 6(8), 1001056. https://doi.org/10.1371/journal.pgen.1001056
Sternberg, P. W. (1988). Lateral inhibition during vulval induction in Caenorhabditis elegans. Nature, 335(6190), 551–554. https://doi.org/10.1038/335551a0
Sternberg, P. W. (2005). Vulval development. In WormBook : the online review of C. elegans biology (pp. 1–28). WormBook. https://doi.org/10.1895/wormbook.1.6.1
Sternberg, P. W., & Horvitz, H. R. (1986). Pattern formation during vulval development in C. elegans. Cell, 44(5), 761–772. https://doi.org/10.1016/0092-8674(86)90842-1
Sulston, J. E., Schierenberg, E., White, J. G., & Thomson, J. N. (1983). The embryonic cell lineage of the nematode Caenorhabditis elegans. In Developmental Biology (Vol. 100, Issue 1, pp. 64–119). https://doi.org/10.1016/0012-1606(83)90201-4
Vitorino, P., & Meyer, T. (2008). Modular control of endothelial sheet migration. Genes & Development, 22(23), 3268–3281. https://doi.org/10.1101/GAD.1725808
Watts, J. L., Etemad-Moghadam, B., Guo, S., Boyd, L., Draper, B. W., Mello, C. C., Priess, J. R., & Kemphues, K. J. (1996). par-6, a gene involved in the establishment of asymmetry in early C. elegans embryos, mediates the asymmetric localization of PAR-3. Development, 122(10), 3133–3140. https://doi.org/10.1242/dev.122.10.3133
Wernike, D., Chen, Y., Mastronardi, K., Makil, N., & Piekny, A. (2016). Mechanical forces drive neuroblast morphogenesis and are required for epidermal closure. Developmental Biology, 412(2), 261–277. https://doi.org/10.1016/j.ydbio.2016.02.023
White, J. G., Southgate, E., Thomson, J. N., & Brenner, S. (1986). The structure of the nervous system of the nematode Caenorhabditis elegans. Philosophical Transactions of the Royal Society of London. B, Biological Sciences, 314(1165), 1–340. https://doi.org/10.1098/rstb.1986.0056
Williams-Masson, E. M., Heid, P. J., Lavin, C. A., & Hardin, J. (1998). The cellular mechanism of epithelial rearrangement during morphogenesis of the Caenorhabditis elegans dorsal hypodermis. Developmental Biology, 204(1), 263–276. https://doi.org/10.1006/dbio.1998.9048
Williams-Masson, E. M., Malik, A. N., & Hardin, J. (1997). An actin-mediated two-step mechanism is required for ventral enclosure of the C. elegans hypodermis. Development, 124(15), 2889–2901. https://doi.org/10.1242/dev.124.15.2889
Williams, B. D., & Waterston, R. H. (1994). Genes critical for muscle development and function in Caenorhabditis elegans identified through lethal mutations. Journal of Cell Biology, 124(4), 475–490. https://doi.org/10.1083/jcb.124.4.475
Zallen, J. A., Kirch, S. A., & Bargmann, C. I. (1999). Genes required for axon pathfinding and extension in the C. elegans nerve ring. Development, 126(16), 3679–3692. https://doi.org/10.1242/DEV.126.16.3679
Zallen, J. A., Yi, B. A., & Bargmann, C. I. (1998). The Conserved Immunoglobulin Superfamily Member SAX-3/Robo Directs Multiple Aspects of Axon Guidance in C. elegans. Cell, 92(2), 217–227. https://doi.org/10.1016/S0092-8674(00)80916-2
Zecca, M., Basler, K., & Struhl, G. (1996). Direct and long-range action of a wingless morphogen gradient. Cell, 87(5), 833–844. https://doi.org/10.1016/S0092-8674(00)81991-1
Zhang, L., Ward, J. D., Cheng, Z., & Dernburg, A. F. (2015). The auxin-inducible degradation (AID) system enables versatile conditional protein depletion in C. elegans. Development, 142(24), 4374–4384. https://doi.org/10.1242/DEV.129635
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