Abstract
We have investigated the role chondroitin sulfate has on cell interactions during neural plate formation in the early chick embryo. Using tissue culture isolates from the prospective neural plate, we have measured neural gene expression profiles associated with neural stem cell differentiation. Removal of chondroitin sulfate from stage 4 neural plate tissue leads to altered associations of N-cadherin-positive neural progenitors and causes changes in the normal sequence of neural marker gene expression. Absence of chondroitin sulfate in the neural plate leads to reduced Sox2 expression and is accompanied by an increase in the expression of anterior markers of neural regionalization. Results obtained in this study suggest that the presence of chondroitin sulfate in the anterior chick embryo is instrumental in maintaining cells in the neural precursor state.
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Bovolenta P, Mallamaci A, Puelles L, Boncinelli E (1998) Expression pattern of cSix3, a member of the six/sine oculis family of transcription factors. Mech Dev 70:201–203
Brittis PA, Canning DR, Silver J (1992) Chondroitin sulfate as a regulator of neuronal patterning in the retina. Science 255:733–736
Bulow HE, Hobert O (2006) The molecular diversity of glycosaminoglycans shapes animal development. Annu Rev Cell Dev Biol 22:375–407
Canning DR, Cunningham RL (2014) Cell adhesion properties of neural stem cells in the chick embryo. In vitro cellular & developmental biology. Animal. doi:10.1007/s11626-014-9851-1
Canning DR, Amin T, Richard E (2000) Regulation of epiblast cell movements by chondroitin sulfate during gastrulation in the chick. Dev Dyn 219:545–559
Chapman SC, Brown R, Lees L, Schoenwolf GC, Lumsden A (2004) Expression analysis of chick Wnt and frizzled genes and selected inhibitors in early chick patterning. Dev Dyn 229:668–676
Darnell DK, Stark MR, Schoenwolf GC (1999) Timing and cell interactions underlying neural induction in the chick embryo. Development 126:2505–2514
Deepa SS, Umehara Y, Higashiyama S, Itoh N, Sugahara K (2002) Specific molecular interactions of oversulfated chondroitin sulfate E with various heparin-binding growth factors. Implications as a physiological binding partner in the brain and other tissues. J Biol Chem 277:43707–43716
Diez del Corral R, Breitkreuz DN, Storey KG (2002) Onset of neuronal differentiation is regulated by paraxial mesoderm and requires attenuation of FGF signalling. Development 129:1681–1691
Eblaghie MC, Lunn JS, Dickinson RJ, Munsterberg AE, Sanz-Ezquerro JJ, Farrell ER, Mathers J, Keyse SM, Storey K, Tickle C (2003) Negative feedback regulation of FGF signaling levels by Pyst1/ MKP3 in chick embryos. Curr Biol 13:1009–1018
Eisenmann KM, McCarthy JB, Simpson MA, Keely PJ, Guan JL, Tachibana K, Lim L, Manser E, Furcht LT, Iida J (1999) Melanoma chondroitin sulphate proteoglycan regulates cell spreading through Cdc42, Ack-1 and p130cas. Nat Cell Biol 1:507–513
Esteve P, Morcillo J, Bovolenta P (2000) Early and dynamic expression of cSfrp1 during chick embryo development. Mech Dev 97:217–221
Fernandez-Garre P, Rodriguez-Gallardo L, Alvarez IS, Puelles L (2002) A neural plate fate map at stage HH4 in the chick: methodology and preliminary data. Brain Res Bull 57:293–295
Friedlander DR, Milev P, Karthikeyan L, Margolis RK, Margolis RU, Grumet M (1994) The neuronal chondroitin sulfate proteoglycan neurocan binds to the neural cell adhesion molecules Ng-CAM/L1/NILE and N-CAM, and inhibits neuronal adhesion and neurite outgrowth. J Cell Biol 125:669–680
Gilbert RJ, McKeon RJ, Darr A, Calabro A, Hascall VC, Bellamkonda RV (2005) CS-4,6 is differentially upregulated in glial scar and is a potent inhibitor of neurite extension. Mol Cell Neurosci 29:545–558
Grumet M, Flaccus A, Margolis RU (1993) Functional characterization of chondroitin sulfate proteoglycans of brain: interactions with neurons and neural cell adhesion molecules. J Cell Biol 120:815–824
Hamburger V, Hamilton HL (1992) A series of normal stages in the development of the chick embryo. 1951 [classical article] [see comments]. Dev Dyn 195:231–272
Ida M, Shuo T, Hirano K, Tokita Y, Nakanishi K, Matsui F, Aono S, Fujita H, Fujiwara Y, Kaji T, Oohira A (2006) Identification and functions of chondroitin sulfate in the milieu of neural stem cells. J Biol Chem 281:5982–5991
Izumikawa T, Kitagawa H, Mizuguchi S, Nomura KH, Nomura K, Tamura J, Gengyo-Ando K, Mitani S, Sugahara K (2004) Nematode chondroitin polymerizing factor showing cell-/organ-specific expression is indispensable for chondroitin synthesis and embryonic cell division. J Biol Chem 279:53755–53761
Izumikawa T, Sato B, Kitagawa H (2014) Chondroitin sulfate is indispensable for pluripotency and differentiation of mouse embryonic stem cells. Sci Rep 4:3701
Joyner AL, Liu A, Millet S (2000) Otx2, Gbx2 and Fgf8 interact to position and maintain a mid-hindbrain organizer. Curr Opin Cell Biol 12:736–741
Kobayashi D, Kobayashi M, Matsumoto K, Ogura T, Nakafuku M, Shimamura K (2002) Early subdivisions in the neural plate define distinct competence for inductive signals. Development 129:83–93
Lagutin OV, Zhu CC, Kobayashi D, Topczewski J, Shimamura K, Puelles L, Russell HR, McKinnon PJ, Solnica-Krezel L, Oliver G (2003) Six3 repression of Wnt signaling in the anterior neuroectoderm is essential for vertebrate forebrain development. Genes Dev 17:368–379
Li H, Leung TC, Hoffman S, Balsamo J, Lilien J (2000) Coordinate regulation of cadherin and integrin function by the chondroitin sulfate proteoglycan neurocan. J Cell Biol 149:1275–1288
Li F, Shetty AK, Sugahara K (2007) Neuritogenic activity of chondroitin/dermatan sulfate hybrid chains of embryonic pig brain and their mimicry from shark liver. Involvement of the pleiotrophin and hepatocyte growth factor signaling pathways. J Biol Chem 282:2956–2966
Margolis RU, Margolis RK (1997) Chondroitin sulfate proteoglycans as mediators of axon growth and pathfinding. Cell Tissue Res 290:343–348
McKeon RJ, Schreiber RC, Rudge JS, Silver J (1991) Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes. J Neurosci 11:3398–3411
Newgreen DF, Powell ME, Moser B (1990) Spatiotemporal changes in HNK-1/L2 glycoconjugates on avian embryo somite and neural crest cells. Dev Biol 139:100–120
Perrimon N, Bernfield M (2000) Specificities of heparan sulphate proteoglycans in developmental processes. Nature 404:725–728
Perrimon N, Bernfield M (2001) Cellular functions of proteoglycans—an overview. Semin Cell Dev Biol 12:65–67
Perris R, Lofberg J, Fallstrom C, von Boxberg Y, Olsson L, Newgreen DF (1990) Structural and compositional divergencies in the extracellular matrix encountered by neural crest cells in the white mutant axolotl embryo. Development 109:533–551
Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29, e45
Pimenta AF, Strick PL, Levitt P (2001) Novel proteoglycan epitope expressed in functionally discrete patterns in primate cortical and subcortical regions. J Comp Neurol 430:369–388
Pires Neto MA, Braga-de-Souza S, Lent R (1999) Extracellular matrix molecules play diverse roles in the growth and guidance of central nervous system axons. Braz J Med Biol Res 32:633–638
Rauch U (1997) Modeling an extracellular environment for axonal pathfinding and fasciculation in the central nervous system. Cell Tissue Res 290:349–356
Rauch U, Karthikeyan L, Maurel P, Margolis RU, Margolis RK (1992) Cloning and primary structure of neurocan, a developmentally regulated, aggregating chondroitin sulfate proteoglycan of brain. J Biol Chem 267:19536–19547
Rauch U, Feng K, Zhou XH (2001) Neurocan: a brain chondroitin sulfate proteoglycan. Cell Mol Life Sci 58:1842–1856
Retzler C, Gohring W, Rauch U (1996) Analysis of neurocan structures interacting with the neural cell adhesion molecule N-CAM. J Biol Chem 271:27304–27310
Rex M, Orme A, Uwanogho D, Tointon K, Wigmore PM, Sharpe PT, Scotting PJ (1997) Dynamic expression of chicken Sox2 and Sox3 genes in ectoderm induced to form neural tissue. Dev Dyn 209:323–332
Schweitzer R, Tabin CJ (1999) The dynamic organizer. Nat Cell Biol 1:E179–E181
Selleck SB (2000) Proteoglycans and pattern formation: sugar biochemistry meets developmental genetics. Trends Genet 16:206–212
Sirko S, von Holst A, Wizenmann A, Gotz M, Faissner A (2007) Chondroitin sulfate glycosaminoglycans control proliferation, radial glia cell differentiation and neurogenesis in neural stem/progenitor cells. Development 134:2727–2738
Sirko S, Akita K, Von Holst A, Faissner A (2008) Structural and functional analysis of chondroitin sulfate proteoglycans in the neural stem cell niche. Methods Enzymol 479:37–71
Sirko S, von Holst A, Weber A, Wizenmann A, Theocharidis U, Gotz M, Faissner A (2010) Chondroitin sulfates are required for fibroblast growth factor-2-dependent proliferation and maintenance in neural stem cells and for epidermal growth factor-dependent migration of their progeny. Stem Cells 28:775–787
Snow DM, Watanabe M, Letourneau PC, Silver J (1991) A chondroitin sulfate proteoglycan may influence the direction of retinal ganglion cell outgrowth. Development 113:1473–1485
Sobel RA, Ahmed AS (2001) White matter extracellular matrix chondroitin sulfate/dermatan sulfate proteoglycans in multiple sclerosis. J Neuropathol Exp Neurol 60:1198–1207
Stacey M, Chang GW, Davies JQ, Kwakkenbos MJ, Sanderson RD, Hamann J, Gordon S, Lin HH (2003) The epidermal growth factor-like domains of the human EMR2 receptor mediate cell attachment through chondroitin sulfate glycosaminoglycans. Blood 102:2916–2924
Stern CD (2002) Induction and initial patterning of the nervous system - the chick embryo enters the scene. Curr Opin Genet Dev 12:447–451
Stern CD (2005) Neural induction: old problem, new findings, yet more questions. Development 132:2007–2021
Storey KG, Goriely A, Sargent CM, Brown JM, Burns HD, Abud HM, Heath JK (1998) Early posterior neural tissue is induced by FGF in the chick embryo. Development 125:473–484
Takemoto T, Uchikawa M, Kamachi Y, Kondoh H (2006) Convergence of Wnt and FGF signals in the genesis of posterior neural plate through activation of the Sox2 enhancer N-1. Development 133:297–306
Talts U, Kuhn U, Roos G, Rauch U (2000) Modulation of extracellular matrix adhesiveness by neurocan and identification of its molecular basis. Exp Cell Res 259:378–388
Tan SS, Prieto AL, Newgreen DF, Crossin KL, Edelman GM (1991) Cytotactin expression in somites after dorsal neural tube and neural crest ablation in chicken embryos. Proc Natl Acad Sci U S A 88:6398–6402
Williamson DA, Parrish EP, Edelman GM (1991) Distribution and expression of two interactive extracellular matrix proteins, cytotactin and cytotactin-binding proteoglycan, during development of Xenopus laevis. I. Embryonic development. J Morphol 209:189–202
Wittler L, Kessel M (2004) The acquisition of neural fate in the chick. Mech Dev 121:1031–1042
Zou P, Zou K, Muramatsu H, Ichihara-Tanaka K, Habuchi O, Ohtake S, Ikematsu S, Sakuma S, Muramatsu T (2003) Glycosaminoglycan structures required for strong binding to midkine, a heparin-binding growth factor. Glycobiology 13:35–42
Acknowledgments
We greatly appreciate the provision of probe DNA from the labs of Diana Darnell, Paola Bovelenta, and Michael Kessel. Christian Clark and Satinder Sidhu contributed technical assistance.
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Editor: Tetsuji Okamoto
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Canning, D.R., Brelsford, N.R. & Lovett, N.W. Chondroitin sulfate effects on neural stem cell differentiation. In Vitro Cell.Dev.Biol.-Animal 52, 35–44 (2016). https://doi.org/10.1007/s11626-015-9941-8
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DOI: https://doi.org/10.1007/s11626-015-9941-8