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Wnt Signaling Polarizes C. elegans Asymmetric Cell Divisions During Development

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Asymmetric Cell Division in Development, Differentiation and Cancer

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 61))

Abstract

Asymmetric cell division is a common mode of cell differentiation during the invariant lineage of the nematode, C. elegans. Beginning at the four-cell stage, and continuing throughout embryogenesis and larval development, mother cells are polarized by Wnt ligands, causing an asymmetric inheritance of key members of a Wnt/β-catenin signal transduction pathway termed the Wnt/β-catenin asymmetry pathway. The resulting daughter cells are distinct at birth with one daughter cell activating Wnt target gene expression via β-catenin activation of TCF, while the other daughter displays transcriptional repression of these target genes. Here, we seek to review the body of evidence underlying a unified model for Wnt-driven asymmetric cell division in C. elegans, identify global themes that occur during asymmetric cell division, as well as highlight tissue-specific variations. We also discuss outstanding questions that remain unanswered regarding this intriguing mode of asymmetric cell division.

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References

  • Altun ZF, Hall D (2009) Epithelial system, seam cells. WormAtlas

    Google Scholar 

  • Austin J, Kenyon C (1994) Cell contact regulates neuroblast formation in the Caenorhabditis elegans lateral epidermis. Development 120:313–323

    CAS  PubMed  Google Scholar 

  • Austin J, Kimble J (1987) glp-1 is required in the germ line for regulation of the decision between mitosis and meiosis in C. elegans. Cell 51:589–599

    Article  CAS  PubMed  Google Scholar 

  • Axelrod JD, Matsuno K, Artavanis-Tsakonas S, Perrimon N (1996) Interaction between wingless and Notch signaling pathways mediated by Dishevelled. Science 271:1826–1832

    Article  CAS  PubMed  Google Scholar 

  • Baldwin AT, Phillips BT (2014) The tumor suppressor APC differentially regulates multiple beta-catenins through the function of axin and CKIalpha during C. elegans asymmetric stem cell divisions. J Cell Sci 127:2771–2781

    Article  CAS  PubMed  Google Scholar 

  • Baldwin AT, Clemons AM, Phillips BT (2016) Unique and redundant beta-catenin regulatory roles of two Dishevelled paralogs during C. elegans asymmetric cell division. J Cell Sci 129:983–993

    Article  CAS  PubMed  Google Scholar 

  • Banerjee D, Chen X, Lin SY, Slack FJ (2010) kin-19/casein kinase Ialpha has dual functions in regulating asymmetric division and terminal differentiation in C. elegans epidermal stem cells. Cell Cycle 9:4748–4765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barker N, Hurlstone A, Musisi H, Miles A, Bienz M, Clevers H (2001) The chromatin remodelling factor Brg-1 interacts with beta-catenin to promote target gene activation. EMBO J 20:4935–4943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barth AI, Caro-Gonzalez HY, Nelson WJ (2008) Role of adenomatous polyposis coli (APC) and microtubules in directional cell migration and neuronal polarization. Semin Cell Dev Biol 19:245–251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bayly R, Axelrod JD (2011) Pointing in the right direction: new developments in the field of planar cell polarity. Nat Rev Genet 12:385–391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bertrand V, Hobert O (2009a) Linking asymmetric cell division to the terminal differentiation program of postmitotic neurons in C. elegans. Dev Cell 16:563–575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bertrand V, Hobert O (2009b) Wnt asymmetry and the terminal division of neuronal progenitors. Cell Cycle 8:1973–1974

    Article  CAS  PubMed  Google Scholar 

  • Bertrand V, Hobert O (2010) Lineage programming: navigating through transient regulatory states via binary decisions. Curr Opin Genet Dev 20:362–368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bhambhani C, Ravindranath AJ, Mentink RA, Chang MV, Betist MC, Yang YX, Koushika SP, Korswagen HC, Cadigan KM (2014) Distinct DNA binding sites contribute to the TCF transcriptional switch in C. elegans and Drosophila. PLoS Genet 10:e1004133

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bilic J, Huang YL, Davidson G, Zimmermann T, Cruciat CM, Bienz M, Niehrs C (2007) Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation. Science 316:1619–1622

    Article  CAS  PubMed  Google Scholar 

  • Bischoff M, Schnabel R (2006) A posterior centre establishes and maintains polarity of the Caenorhabditis elegans embryo by a Wnt-dependent relay mechanism. PLoS Biol 4:e396

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Brocardo M, Lei Y, Tighe A, Taylor SS, Mok MT, Henderson BR (2008) Mitochondrial targeting of adenomatous polyposis coli protein is stimulated by truncating cancer mutations: regulation of Bcl-2 and implications for cell survival. J Biol Chem 283:5950–5959

    Article  CAS  PubMed  Google Scholar 

  • Brunner E, Peter O, Schweizer L, Basler K (1997) pangolin encodes a Lef-1 homologue that acts downstream of Armadillo to transduce the Wingless signal in Drosophila. Nature 385:829–833

    Article  CAS  PubMed  Google Scholar 

  • Byrd DT, Knobel K, Affeldt K, Crittenden SL, Kimble J (2014) A DTC niche plexus surrounds the germline stem cell pool in Caenorhabditis elegans. PLoS One 9:e88372

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Calvo D, Victor M, Gay F, Sui G, Luke MP-S, Dufourcq P, Wen G, Maduro M, Rothman J, Shi Y (2001) A POP-1 repressor complex restricts inappropriate cell type-specific gene transcription during Caenorhabditis elegans embryogenesis. EMBO J 20:7197–7208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang W, Lloyd CE, Zarkower D (2005) DSH-2 regulates asymmetric cell division in the early C. elegans somatic gonad. Mech Dev 122:781–789

    Article  CAS  PubMed  Google Scholar 

  • Chesney MA, Lam N, Morgan DE, Phillips BT, Kimble J (2009) C. elegans HLH-2/E/Daughterless controls key regulatory cells during gonadogenesis. Dev Biol 331:14–25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clevers H, Nusse R (2012) Wnt/beta-catenin signaling and disease. Cell 149:1192–1205

    Article  CAS  PubMed  Google Scholar 

  • Deshpande R, Inoue T, Priess JR, Hill RJ (2005) lin-17/Frizzled and lin-18 regulate POP-1/TCF-1 localization and cell type specification during C. elegans vulval development. Dev Biol 278:118–129

    Article  CAS  PubMed  Google Scholar 

  • Ehaideb SN, Iyengar A, Ueda A, Iacobucci GJ, Cranston C, Bassuk AG, Gubb D, Axelrod JD, Gunawardena S, Wu CF, Manak JR (2014) prickle modulates microtubule polarity and axonal transport to ameliorate seizures in flies. Proc Natl Acad Sci USA 111:11187–11192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eisenmann D (2005) Wnt signaling. WormBook [Online]. Available: http://www.wormbook.org. Accessed 25 Jun 2005

  • Eisenmann DM (2011) C. elegans seam cells as stem cells: Wnt signaling and casein kinase Ialpha regulate asymmetric cell divisions in an epidermal progenitor cell type. Cell Cycle 10:20–21

    Article  CAS  PubMed  Google Scholar 

  • Eisenmann DM, Maloof JN, Simske JS, Kenyon C, Kim SK (1998) The β-catenin homolog BAR-1 and LET-60 Ras coordinately regulate the Hox gene lin-39 during Caenorhabditis elegans vulval development. Development 125:3667–3680

    CAS  PubMed  Google Scholar 

  • Fabunmi RP, Wigley WC, Thomas PJ, DeMartino GN (2000) Activity and regulation of the centrosome-associated proteasome. J Biol Chem 275:409–413

    Article  CAS  PubMed  Google Scholar 

  • Gao B (2012) Wnt regulation of planar cell polarity (PCP). Curr Top Dev Biol 101:263–295

    Article  CAS  PubMed  Google Scholar 

  • Gao C, Chen YG (2010) Dishevelled: the hub of Wnt signaling. Cell Signal 22:717–727

    Article  CAS  PubMed  Google Scholar 

  • Gleason JE, Eisenmann DM (2010) Wnt signaling controls the stem cell-like asymmetric division of the epithelial seam cells during C. elegans larval development. Dev Biol 348:58–66

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gleason JE, Szyleyko EA, Eisenmann DM (2006) Multiple redundant Wnt signaling components function in two processes during C. elegans vulval development. Dev Biol 298:442–457

    Article  CAS  PubMed  Google Scholar 

  • Goldstein B (1992) Induction of gut in Caenorhabditis elegans embryos. Nature 357:255–257

    Article  CAS  PubMed  Google Scholar 

  • Goldstein B (1993) Establishment of gut fate in the E lineage of C. elegans: the roles of lineage-dependent mechanisms and cell interactions. Development 118:1267–1277

    CAS  PubMed  Google Scholar 

  • Goldstein B, Hird SN (1996) Specification of the anteroposterior axis in Caenorhabditis elegans. Development 122:1467–1474

    CAS  PubMed  Google Scholar 

  • Goldstein B, Takeshita H, Mizumoto K, Sawa H (2006) Wnt signals can function as positional cues in establishing cell polarity. Dev Cell 10:391–396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gorrepati L, Eisenmann DM (2015) The C. elegans embryonic fate specification factor EGL-18 (GATA) is reutilized downstream of Wnt signaling to maintain a population of larval progenitor cells. Worm 4:e996419

    Google Scholar 

  • Gorrepati L, Thompson KW, Eisenmann DM (2013) C. elegans GATA factors EGL-18 and ELT-6 function downstream of Wnt signaling to maintain the progenitor fate during larval asymmetric divisions of the seam cells. Development 140:2093–2102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gorrepati L, Krause MW, Chen W, Brodigan TM, Correa-Mendez M, Eisenmann DM (2015) Identification of Wnt pathway target genes regulating the division and differentiation of larval seam cells and vulval precursor cells in Caenorhabditis elegans. G3 (Bethesda) 5:1551–1566

    Article  Google Scholar 

  • Green RA, Kaplan KB (2003) Chromosome instability in colorectal tumor cells is associated with defects in microtubule plus-end attachments caused by a dominant mutation in APC. J Cell Biol 163:949–961

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Green JL, Inoue T, Sternberg PW (2008) Opposing Wnt pathways orient cell polarity during organogenesis. Cell 134:646–656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Habib SJ, Chen BC, Tsai FC, Anastassiadis K, Meyer T, Betzig E, Nusse R (2013) A localized Wnt signal orients asymmetric stem cell division in vitro. Science 339:1445–1448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hajduskova M, Jindra M, Herman MA, Asahina M (2009) The nuclear receptor NHR-25 cooperates with the Wnt/beta-catenin asymmetry pathway to control differentiation of the T seam cell in C. elegans. J Cell Sci 122:3051–3060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harandi OF, Ambros VR (2015) Control of stem cell self-renewal and differentiation by the heterochronic genes and the cellular asymmetry machinery in Caenorhabditis elegans. Proc Natl Acad Sci USA 112:E287–E296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hardin J, King RS (2008) The long and the short of Wnt signaling in C. elegans. Curr Opin Genet Dev 18:362–367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hart MJ, de los Santos R, Albert IN, Rubinfeld B, Polakis P (1998) Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta. Curr Biol 8:573–581

    Article  CAS  PubMed  Google Scholar 

  • Harterink M, Korswagen HC (2012) Dissecting the Wnt secretion pathway: key questions on the modification and intracellular trafficking of Wnt proteins. Acta Physiol (Oxf) 204:8–16

    Article  CAS  Google Scholar 

  • Harterink M, Kim DH, Middelkoop TC, Doan TD, van Oudenaarden A, Korswagen HC (2011) Neuroblast migration along the anteroposterior axis of C. elegans is controlled by opposing gradients of Wnts and a secreted Frizzled-related protein. Development 138:2915–2924

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hecht A, Vleminckx K, Stemmler MP, van Roy F, Kemler R (2000) The p300/CBP acetyltransferases function as transcriptional coactivators of beta-catenin in vertebrates. EMBO J 19:1839–1850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Herman MA (2002) Control of cell polarity by noncanonical Wnt signaling in C. elegans. Semin Cell Dev Biol 13:233–241

    Article  CAS  PubMed  Google Scholar 

  • Herman MA, Vassilieva LL, Horvitz HR, Shaw JE, Herman RK (1995) The C. elegans gene lin-44, which controls the polarity of certain asymmetric cell divisions, encodes a Wnt protein and acts cell nonautonomously. Cell 83:101–110

    Article  CAS  PubMed  Google Scholar 

  • Hingwing K, Lee S, Nykilchuk L, Walston T, Hardin J, Hawkins N (2009) CWN-1 functions with DSH-2 to regulate C. elegans asymmetric neuroblast division in a beta-catenin independent Wnt pathway. Dev Biol 328:245–256

    Article  CAS  PubMed  Google Scholar 

  • Huang S, Shetty P, Robertson SM, Lin R (2007) Binary cell fate specification during C. elegans embryogenesis driven by reiterated reciprocal asymmetry of TCF POP-1 and its coactivator β-catenin SYS-1. Development 134:2685–2695

    Article  CAS  PubMed  Google Scholar 

  • Huber AH, Nelson WJ, Weis WI (1997) Three-dimensional structure of the armadillo repeat region of β-catenin. Cell 90:871–882

    Article  CAS  PubMed  Google Scholar 

  • Ikeda S, Kishida S, Yamamoto H, Murai H, Koyama S, Kikuchi A (1998) Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin. EMBO J 17:1371–1384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Inoue T, Oz HS, Wiland D, Gharib S, Deshpande R, Hill RJ, Katz WS, Sternberg PW (2004) C. elegans LIN-18 is a Ryk ortholog and functions in parallel to LIN-17/Frizzled in Wnt signaling. Cell 118:795–806

    Article  CAS  PubMed  Google Scholar 

  • Ishitani T, Ninomiya-Tsuji J, Nagai S-I, Nishita M, Meneghini M, Barker N, Waterman M, Bowerman B, Clevers H, Shibuya H, Matsumoto K (1999) The TAK1-NLK-MAPK-related pathway antagonizes signalling between β-catenin and transcription factor TCF. Nature 399:798–802

    Article  CAS  PubMed  Google Scholar 

  • Jackson BM, Eisenmann DM (2012) beta-catenin-dependent Wnt signaling in C. elegans: teaching an old dog a new trick. Cold Spring Harb Perspect Biol 4:a007948

    Google Scholar 

  • Jho E, Lomvardas S, Costantini F (1999) A GSK3beta phosphorylation site in axin modulates interaction with beta-catenin and Tcf-mediated gene expression. Biochem Biophys Res Commun 266:28–35

    Article  CAS  PubMed  Google Scholar 

  • Jiang LI, Sternberg PW (1999) An HMG1-like protein facilitates Wnt signaling in Caenorhabditis elegans. Genes Dev 13:877–889

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaletta T, Schnabel H, Schnabel R (1997) Binary specification of the embryonic lineage in Caenorhabditis elegans. Nature 390:294–298

    Article  CAS  PubMed  Google Scholar 

  • Kidd AR 3rd, Miskowski JA, Siegfried KR, Sawa H, Kimble J (2005) A β-catenin identified by functional rather than sequence criteria and its role in Wnt/MAPK signaling. Cell 121:761–772

    Article  CAS  PubMed  Google Scholar 

  • Kidd AR 3rd, Muniz-Medina V, Der CJ, Cox AD, Reiner DJ (2015) The C. elegans Chp/Wrch Ortholog CHW-1 Contributes to LIN-18/Ryk and LIN-17/Frizzled signaling in cell polarity. PLoS One 10:e0133226

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kimble J (1981) Alterations in cell lineage following laser ablation of cells in the somatic gonad of Caenorhabditis elegans. Dev Biol 87:286–300

    Article  CAS  PubMed  Google Scholar 

  • Kimble J, Hirsh D (1979) The postembryonic cell lineages of the hermaphrodite and male gonads in Caenorhabditis elegans. Dev Biol 70:396–417

    Article  CAS  PubMed  Google Scholar 

  • Kimble J, Ward S (1988) Germ-line development and fertilization. In: Wood WB (ed) The nematode Caenorhabditis elegans. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY

    Google Scholar 

  • King RS, Maiden SL, Hawkins NC, Kidd AR 3rd, Kimble J, Hardin J, Walston TD (2009) The N- or C-terminal domains of DSH-2 can activate the C. elegans Wnt/β-catenin asymmetry pathway. Dev Biol 328:234–244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klein TJ, Mlodzik M (2005) Planar cell polarization: an emerging model points in the right direction. Annu Rev Cell Dev Biol 21:155–176

    Article  CAS  PubMed  Google Scholar 

  • Korswagen HC, Herman MA, Clevers HC (2000) Distinct β-catenins mediate adhesion and signalling functions in C. elegans. Nature 406:527–532

    Article  CAS  PubMed  Google Scholar 

  • Kramps T, Peter O, Brunner E, Nellen D, Froesch B, Chatterjee S, Murone M, Züllig S, Basler K (2002) WNT/Wingless signaling requires BCL9/Legless-mediated recruitment of Pygopus to the nuclear β-catenin-TCF complex. Cell 109:47–60

    Article  CAS  PubMed  Google Scholar 

  • Lam N, Chesney MA, Kimble J (2006) Wnt signaling and CEH-22/tinman/Nkx2.5 specify a stem cell niche in C. elegans. Curr Biol 16:287–295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leung JY, Kolligs FT, Wu R, Zhai Y, Kuick R, Hanash S, Cho KR, Fearon ER (2002) Activation of AXIN2 expression by beta-catenin-T cell factor. A feedback repressor pathway regulating Wnt signaling. J Biol Chem 277:21657–21665

    Article  CAS  PubMed  Google Scholar 

  • Lin R, Thompson S, Priess JR (1995) pop-1 encodes an HMG box protein required for the specification of a mesoderm precursor in early C. elegans embryos. Cell 83:599–609

    Article  CAS  PubMed  Google Scholar 

  • Lin R, Hill RJ, Priess JR (1998) POP-1 and anterior-posterior fate decision in C. elegans embryos. Cell 92:229–239

    Article  CAS  PubMed  Google Scholar 

  • Lin S, Baye LM, Westfall TA, Slusarski DC (2010) Wnt5b-Ryk pathway provides directional signals to regulate gastrulation movement. J Cell Biol 190:263–278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu J, Phillips BT, Amaya MF, Kimble J, Xu W (2008) The C. elegans SYS-1 protein is a bona fide β-catenin. Dev Cell 14:751–761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lo M-C, Gay F, Odom R, Shi Y, Lin R (2004) Phosphorylation by the β-catenin/MAPK complex promotes 14-3-3-mediated nuclear export of TCF/POP-1 in signal-responsive cells in C. elegans. Cell 117:95–106

    Article  CAS  PubMed  Google Scholar 

  • Logan CY, Nusse R (2004) The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 20:781–810

    Article  CAS  PubMed  Google Scholar 

  • MacDonald BT, He X (2012) Frizzled and LRP5/6 receptors for Wnt/beta-catenin signaling. Cold Spring Harb Perspect Biol 4:1–23

    Google Scholar 

  • Maduro MF, Lin R, Rothman JH (2002) Dynamics of a developmental switch: recursive intracellular and intranuclear redistribution of Caenorhabditis elegans POP-1 parallels Wnt-inhibited transcriptional repression. Dev Biol 248:128–142

    Article  CAS  PubMed  Google Scholar 

  • Maduro MF, Kasmir JJ, Zhu J, Rothman JH (2005) The Wnt effector POP-1 and the PAL-1/Caudal homeoprotein collaborate with SKN-1 to activate C. elegans endoderm development. Dev Biol 285:510–523

    Article  CAS  PubMed  Google Scholar 

  • Mayor R, Theveneau E (2014) The role of the non-canonical Wnt-planar cell polarity pathway in neural crest migration. Biochem J 457:19–26

    Article  CAS  PubMed  Google Scholar 

  • Meneghini MD, Ishitani T, Carter JC, Hisamoto N, Ninomiya-Tsuji J, Thorpe CJ, Hamill DR, Matsumoto K, Bowerman B (1999) MAP kinase and Wnt pathways converge to downregulate an HMG-domain repressor in Caenorhabditis elegans. Nature 399:793–797

    Article  CAS  PubMed  Google Scholar 

  • Mila D, Calderon A, Baldwin AT, Moore KM, Watson M, Phillips BT, Putzke AP (2015) Asymmetric Wnt pathway signaling facilitates stem cell-like divisions via the nonreceptor tyrosine kinase FRK-1 in Caenorhabditis elegans. Genetics 201:1047–1060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mimori-Kiyosue Y, Shiina N, Tsukita S (2000) The dynamic behavior of the APC-binding protein EB1 on the distal ends of microtubules. Curr Biol 10:865–868

    Article  CAS  PubMed  Google Scholar 

  • Miskowski J, Li Y, Kimble J (2001) The sys-1 gene and sexual dimorphism during gonadogenesis in Caenorhabditis elegans. Dev Biol 230:61–73

    Article  CAS  PubMed  Google Scholar 

  • Mizumoto K, Sawa H (2007a) Cortical β-catenin and APC regulate asymmetric nuclear β-catenin localization during asymmetric cell division in C. elegans. Dev Cell 12:287–299

    Article  CAS  PubMed  Google Scholar 

  • Mizumoto K, Sawa H (2007b) Two βs or not two βs: regulation of asymmetric division by β-catenin. Trends Cell Biol 17:465–473

    Article  CAS  PubMed  Google Scholar 

  • Molenaar M, van de Wetering M, Oosterwegel M, Peterson-Maduro J, Godsave S, Korinek V, Roose J, Destrée O, Clevers H (1996) XTcf-3 transcription factor mediates β-catenin-induced axis formation in Xenopus embryos. Cell 86:391–399

    Article  CAS  PubMed  Google Scholar 

  • Munro E, Bowerman B (2009) Cellular symmetry breaking during Caenorhabditis elegans development. Cold Spring Harb Perspect Biol 1:a003400

    Article  PubMed  PubMed Central  Google Scholar 

  • Murgan S, Bertrand V (2015) How targets select activation or repression in response to Wnt. Worm 4:e1086869

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Murgan S, Kari W, Rothbacher U, Iche-Torres M, Melenec P, Hobert O, Bertrand V (2015) Atypical transcriptional activation by TCF via a Zic transcription factor in C. elegans neuronal precursors. Dev Cell 33:737–745

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakamura K, Kim S, Ishidate T, Bei Y, Pang K, Shirayama M, Trzepacz C, Brownell DR, Mello CC (2005) Wnt signaling drives WRM-1/β-catenin asymmetries in early C. elegans embryos. Genes Dev 19:1749–1754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Natarajan L, Witwer NE, Eisenmann DM (2001) The divergent Caenorhabditis elegans β-catenin proteins BAR-1, WRM-1 and HMP-2 make distinct protein interactions but retain functional redundancy in vivo. Genetics 159:159–172

    CAS  PubMed  PubMed Central  Google Scholar 

  • Park FD, Priess JR (2003) Establishment of POP-1 asymmetry in early C. elegans embryos. Development 130:3547–3556

    Article  CAS  PubMed  Google Scholar 

  • Park FD, Tenlen JR, Priess JR (2004) C. elegans MOM-5/frizzled functions in MOM-2/Wnt-independent cell polarity and is localized asymmetrically prior to cell division. Curr Biol 14:2252–2258

    Article  CAS  PubMed  Google Scholar 

  • Parker DS, Jemison J, Cadigan KM (2002) Pygopus, a nuclear PHD-finger protein required for Wingless signaling in Drosophila. Development 129:2565–2576

    CAS  PubMed  Google Scholar 

  • Phillips BT, Kimble J (2009) A new look at TCF and β-catenin through the lens of a divergent C. elegans Wnt pathway. Dev Cell 17:27–34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Phillips BT, Kidd AR 3rd, King R, Hardin J, Kimble J (2007) Reciprocal asymmetry of SYS-1/beta-catenin and POP-1/TCF controls asymmetric divisions in Caenorhabditis elegans. Proc Natl Acad Sci USA 104:3231–3236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poy F, Lepourcelet M, Shivdasani RA, Eck MJ (2001) Structure of a human Tcf4-β-catenin complex. Nat Struct Biol 8:1053–1057

    Article  CAS  PubMed  Google Scholar 

  • Ravindranath AJ, Cadigan KM (2014) Structure-function analysis of the C-clamp of TCF/Pangolin in Wnt/ss-catenin signaling. PLoS One 9:e86180

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rocheleau CE, Downs WD, Lin R, Wittmann C, Bei Y, Cha Y-H, Ali M, Priess JR, Mello CC (1997) Wnt signaling and an APC-related gene specify endoderm in early C. elegans embryos. Cell 90:707–716

    Article  CAS  PubMed  Google Scholar 

  • Rocheleau CE, Yasuda J, Shin TH, Lin R, Sawa H, Okano H, Priess JR, Davis RJ, Mello CC (1999) WRM-1 activates the LIT-1 protein kinase to transduce anterior/posterior polarity signals in C. elegans. Cell 97:717–726

    Article  CAS  PubMed  Google Scholar 

  • Roose J, Clevers H (1999) TCF transcription factors: molecular switches in carcinogenesis. Biochim Biophys Acta 97456:M23–M37

    Google Scholar 

  • Roose J, Molenaar M, Peterson J, Hurenkamp J, Brantjes H, Moerer P, van de Wetering M, Destree O, Clevers H (1998) The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors. Nature 395:608–612

    Article  CAS  PubMed  Google Scholar 

  • Rose L, Gonczy P (2014) Polarity establishment, asymmetric division and segregation of fate determinants in early C. elegans embryos. WormBook, pp 1–43

    Google Scholar 

  • Rubinfeld B, Albert I, Porfiri E, Fiol C, Munemitsu S, Polakis P (1996) Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly. Science 272:1023–1026

    Article  CAS  PubMed  Google Scholar 

  • Sawa H, Korswagen HC (2013) Wnt signaling in C. elegans. WormBook, pp 1–30

    Google Scholar 

  • Schmid T, Hajnal A (2015) Signal transduction during C. elegans vulval development: a NeverEnding story. Curr Opin Genet Dev 32:1–9

    Article  CAS  PubMed  Google Scholar 

  • Schmidt DJ, Rose DJ, Saxton WM, Strome S (2005) Functional analysis of cytoplasmic dynein heavy chain in Caenorhabditis elegans with fast-acting temperature-sensitive mutations. Mol Biol Cell 16:1200–1212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shetty P, Lo M-C, Robertson SM, Lin R (2005) C. elegans TCF protein, POP-1, converts from repressor to activator as a result of Wnt-induced lowering of nuclear levels. Dev Biol 285:584–592

    Article  CAS  PubMed  Google Scholar 

  • Shin TH, Yasuda J, Rocheleau CE, Lin R, Soto M, Bei Y, Davis RJ, Mello CC (1999) MOM-4, a MAP kinase kinase kinase-related protein, activates WRM-1/LIT- 1 kinase to transduce anterior/posterior polarity signals in C. elegans. Mol Cell 4:275–280

    Article  CAS  PubMed  Google Scholar 

  • Siegfried K, Kimble J (2002) POP-1 controls axis formation during early gonadogenesis in C. elegans. Development 129:443–453

    CAS  PubMed  Google Scholar 

  • Siegfried KR, Kidd AR 3rd, Chesney MA, Kimble J (2004) The sys-1 and sys-3 genes cooperate with Wnt signaling to establish the proximal-distal axis of the Caenorhabditis elegans gonad. Genetics 166:171–186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sokol SY (1999) Wnt signaling and dorso-ventral axis specification in vertebrates. Curr Opin Genet Dev 9:405–410

    Article  CAS  PubMed  Google Scholar 

  • Sokol SY (2015) Spatial and temporal aspects of Wnt signaling and planar cell polarity during vertebrate embryonic development. Semin Cell Dev Biol 42:78–85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song X, Wang S, Li L (2014) New insights into the regulation of Axin function in canonical Wnt signaling pathway. Protein Cell 5:186–193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Strovel ET, Wu D, Sussman DJ (2000) Protein phosphatase 2Calpha dephosphorylates axin and activates LEF-1-dependent transcription. J Biol Chem 275:2399–2403

    Article  CAS  PubMed  Google Scholar 

  • Sugioka K, Sawa H (2010) Regulation of asymmetric positioning of nuclei by Wnt and Src signaling and its roles in POP-1/TCF nuclear asymmetry in Caenorhabditis elegans. Genes Cells 15:397–407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sugioka K, Mizumoto K, Sawa H (2011) Wnt regulates spindle asymmetry to generate asymmetric nuclear beta-catenin in C. elegans. Cell 146:942–954

    Article  CAS  PubMed  Google Scholar 

  • Sulston JE, Horvitz HR (1977) Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dev Biol 56:110–156

    Article  CAS  PubMed  Google Scholar 

  • Takemaru KI, Moon RT (2000) The transcriptional coactivator CBP interacts with beta-catenin to activate gene expression. J Cell Biol 149:249–254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takeshita H, Sawa H (2005) Asymmetric cortical and nuclear localizations of WRM-1/β-catenin during asymmetric cell division in C. elegans. Genes Dev 19:1743–1748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thompson B, Townsley F, Rosin-Arbesfeld R, Musisi H, Bienz M (2002) A new nuclear component of the Wnt signalling pathway. Nat Cell Biol 4:367–373

    Article  CAS  PubMed  Google Scholar 

  • Thorpe CJ, Schlesinger A, Carter JC, Bowerman B (1997) Wnt signaling polarizes an early C. elegans blastomere to distinguish endoderm from mesoderm. Cell 90:695–705

    Article  CAS  PubMed  Google Scholar 

  • Vora S, Phillips BT (2015) Centrosome-associated degradation limits beta-catenin inheritance by daughter cells after asymmetric division. Curr Biol 25:1005–1016

    Article  CAS  PubMed  Google Scholar 

  • Vora SM, Phillips BT (2016) The benefits of local depletion: The centrosome as a scaffold for ubiquitin-proteasome-mediated degradation. Cell Cycle 15:2124–2134

    Article  CAS  PubMed  Google Scholar 

  • Wallingford JB, Mitchell B (2011) Strange as it may seem: the many links between Wnt signaling, planar cell polarity, and cilia. Genes Dev 25:201–213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wehrli M, Tomlinson A (1998) Independent regulation of anterior/posterior and equatorial/polar polarity in the Drosophila eye; evidence for the involvement of Wnt signaling in the equatorial/polar axis. Development 125:1421–1432

    CAS  PubMed  Google Scholar 

  • Wenick AS, Hobert O (2004) Genomic cis-regulatory architecture and trans-acting regulators of a single interneuron-specific gene battery in C. elegans. Dev Cell 6:757–770

    Article  CAS  PubMed  Google Scholar 

  • Wigley WC, Fabunmi RP, Lee MG, Marino CR, Muallem S, DeMartino GN, Thomas PJ (1999) Dynamic association of proteasomal machinery with the centrosome. J Cell Biol 145:481–490

    Article  CAS  PubMed  Google Scholar 

  • Wildwater M, Sander N, de Vreede G, van den Heuvel S (2011) Cell shape and Wnt signaling redundantly control the division axis of C. elegans epithelial stem cells. Development 138:4375–4385

    Article  CAS  PubMed  Google Scholar 

  • Xing Y, Takemaru K, Liu J, Berndt JD, Zheng JJ, Moon RT, Xu W (2008) Crystal structure of a full-length beta-catenin. Structure 16:478–487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamamoto H, Kishida S, Kishida M, Ikeda S, Takada S, Kikuchi A (1999) Phosphorylation of axin, a Wnt signal negative regulator, by glycogen synthase kinase-3beta regulates its stability. J Biol Chem 274:10681–10684

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto Y, Takeshita H, Sawa H (2011) Multiple Wnts redundantly control polarity orientation in Caenorhabditis elegans epithelial stem cells. PLoS Genet 7:e1002308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamashita YM, Jones DL, Fuller MT (2003) Orientation of asymmetric stem cell division by the APC tumor suppressor and centrosome. Science 301:1547–1550

    Article  CAS  PubMed  Google Scholar 

  • Yan D, Wiesmann M, Rohan M, Chan V, Jefferson AB, Guo L, Sakamoto D, Caothien RH, Fuller JH, Reinhard C, Garcia PD, Randazzo FM, Escobedo J, Fantl WJ, Williams LT (2001) Elevated expression of axin2 and hnkd mRNA provides evidence that Wnt/beta -catenin signaling is activated in human colon tumors. Proc Natl Acad Sci USA 98:14973–14978

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang XD, Huang S, Lo MC, Mizumoto K, Sawa H, Xu W, Robertson S, Lin R (2011) Distinct and mutually inhibitory binding by two divergent {beta}-catenins coordinates TCF levels and activity in C. elegans. Development 138:4255–4265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang XD, Karhadkar TR, Medina J, Robertson SM, Lin R (2015) beta-Catenin-related protein WRM-1 is a multifunctional regulatory subunit of the LIT-1 MAPK complex. Proc Natl Acad Sci USA 112:E137–E146

    Article  CAS  PubMed  Google Scholar 

  • Yoda A, Kouike H, Okano H, Sawa H (2005) Components of the transcriptional Mediator complex are required for asymmetric cell division in C. elegans. Development 132:1885–1893

    Article  CAS  PubMed  Google Scholar 

  • Zacharias AL, Murray JI (2016) Combinatorial decoding of the invariant C. elegans embryonic lineage in space and time. Genesis 54:182–197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zacharias AL, Walton T, Preston E, Murray JI (2015) Quantitative differences in nuclear beta-catenin and TCF pattern embryonic cells in C. elegans. PLoS Genet 11:e1005585

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zumbrunn J, Kinoshita K, Hyman AA, Nathke IS (2001) Binding of the adenomatous polyposis coli protein to microtubules increases microtubule stability and is regulated by GSK3 beta phosphorylation. Curr Biol 11:44–49

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank the Phillips lab for helpful comments on the manuscript. This work was supported by the American Cancer Society [grant number RSG-11-140-01-DC], the Roy J. Carver Charitable Trust [grant number 13-4131], and the National Science Foundation [grant number IOS-1456941] to B.T.P.

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Authors and Affiliations

  1. Interdisciplinary Graduate Program in Molecular and Cellular Biology, University of Iowa, Iowa City, IA, USA

    Arielle Koonyee Lam

  2. Department of Biology, University of Iowa, Iowa City, IA, USA

    Bryan T. Phillips

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  1. Arielle Koonyee Lam
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  2. Bryan T. Phillips
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Correspondence to Bryan T. Phillips .

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  1. IGDR, UMR 6290, CNRS, Université de Rennes 1, Rennes, France

    Jean-Pierre Tassan

  2. Inst of Genetics & Dev of Rennes IG, CNRS/Unive Rennes 1 UMR 6290, Rennes Cedex, France

    Jacek Z. Kubiak

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Lam, A.K., Phillips, B.T. (2017). Wnt Signaling Polarizes C. elegans Asymmetric Cell Divisions During Development. In: Tassan, JP., Kubiak, J. (eds) Asymmetric Cell Division in Development, Differentiation and Cancer. Results and Problems in Cell Differentiation, vol 61. Springer, Cham. https://doi.org/10.1007/978-3-319-53150-2_4

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