Purinergic Signalling

, Volume 11, Issue 1, pp 155–160 | Cite as

NTPDase2 and the P2Y1 receptor are not required for mammalian eye formation

  • Kristine GampeEmail author
  • Silke Haverkamp
  • Simon C. Robson
  • Christian Gachet
  • Laura Hüser
  • Amparo Acker-Palmer
  • Herbert Zimmermann
Brief Communication


Eye formation in vertebrates is controlled by a conserved pattern of molecular networks. Homeobox transcription factors are crucially involved in the establishment and maintenance of the retina. A previous study of Massé et al. (Nature, 449: 1058–62, 2007) using morpholino knockdown identified the ectonucleotidase NTPDase2 and the P2Y1 receptor as essential elements for eye formation in embryos of the clawed frog Xenopus laevis. In order to investigate whether a similarly essential mechanism would be active in mammalian eye development, we analyzed mice KO for Entpd2 or P2ry1 as well as double KO for Entpd2/P2ry1. These mice developed normal eyes. In order to identify potential deficits in the molecular identity or in the arrangement of the cellular elements of the retina, we performed an immunohistological analysis using a variety of retinal markers. The analysis of single and double KO mice demonstrated that NTPDase2 and P2Y1 receptors are not required for murine eye formation, as previously shown for eye development in Xenopus laevis.


NTPDase2 ATP ADP P2Y1 receptor Purinergic signaling Eye development 



This work was supported by grants from the Cluster of Excellence EXC 115 and Gutenberg Research College (GCR) Mainz University (to A A-P) and from NIH (R21 CA164970/NCI and HL R01 094400/NHLBI) (to SC R).

Conflict of interest

The authors indicate no potential conflicts of interest.


  1. 1.
    Zimmermann H (2011) Purinergic signaling in neural development. Semin Cell Dev Biol 22:194–204CrossRefPubMedGoogle Scholar
  2. 2.
    Scemes E, Duval N, Meda P (2003) Reduced expression of P2Y1 receptors in connexin43-null mice alters calcium signaling and migration of neural progenitor cells. J Neurosci 23:11444–11452PubMedCentralPubMedGoogle Scholar
  3. 3.
    Mishra SK, Braun N, Shukla V, Füllgrabe M, Schomerus C, Korf H-W, Gachet C, Ikehara Y, Sévigny J, Robson SC, Zimmermann H (2006) Extracellular nucleotide signaling in adult neural stem cells: Synergism with growth factor-mediated cellular proliferation. Development 133:675–684CrossRefPubMedGoogle Scholar
  4. 4.
    Lin JHC, Takano T, Arcuino G, Wang XH, Hu FR, Darzynkiewicz Z, Nunes M, Goldman SA, Nedergaard M (2007) Purinergic signaling regulates neural progenitor cell expansion and neurogenesis. Dev Biol 302:356–366CrossRefPubMedCentralPubMedGoogle Scholar
  5. 5.
    Striedinger K, Meda P, Scemes E (2007) Exocytosis of ATP from astrocyte progenitors modulates spontaneous Ca2+ oscillations and cell migration. Glia 55:652–662CrossRefPubMedCentralPubMedGoogle Scholar
  6. 6.
    Grimm I, Ullsperger SN, Zimmermann H (2010) Nucleotides and epidermal growth factor induce parallel cytoskeletal rearrangements and migration in cultured adult murine neural stem cells. Acta Physiol 199:181–189CrossRefGoogle Scholar
  7. 7.
    Weissman TA, Riquelme PA, Ivic L, Flint AC, Kriegstein AR (2004) Calcium waves propagate through radial glial cells and modulate proliferation in the developing neocortex. Neuron 43:647–661CrossRefPubMedGoogle Scholar
  8. 8.
    Liu XX, Hashimoto-Torii K, Torii M, Haydar TF, Rakic P (2008) The role of ATP signaling in the migration of intermediate neuronal progenitors to the neocortical subventricular zone. Proc Natl Acad Sci U S A 105:11802–11807CrossRefPubMedCentralPubMedGoogle Scholar
  9. 9.
    Liu X, Hashimoto-Torii K, Torii M, Ding C, Rakic P (2010) Gap junctions/hemichannels modulate interkinetic nuclear migration in the forebrain precursors. J Neurosci 30:4197–4209CrossRefPubMedCentralPubMedGoogle Scholar
  10. 10.
    Suyama S, Sunabori T, Kanki H, Sawamoto K, Gachet C, Koizumi S, Okano H (2012) Purinergic signaling promotes proliferation of adult mouse subventricular zone cells. J Neurosci 32:9238–9247CrossRefPubMedGoogle Scholar
  11. 11.
    Boccazzi M, Rolando C, Abbracchio MP, Buffo A, Ceruti S (2014) Purines regulate adult brain subventricular zone cell functions: Contribution of reactive astrocytes. Glia 62:428–439CrossRefPubMedGoogle Scholar
  12. 12.
    Cao X, Li LP, Qin XH, Li SJ, Zhang M, Wang Q, Hu HH, Fang YY, Gao YB, Li XW, Sun LR, Xiong WC, Gao TM, Zhu XH (2013) Astrocytic ATP release regulates the proliferation of neural stem cells in the adult hippocampus. Stem Cells 31:1633–1643CrossRefPubMedGoogle Scholar
  13. 13.
    Gampe K, Stefani J, Hammer K, Brendel P, Pötzsch A, Enikolopov G, Enjyoji K, Acker-Palmer A, Robson SC, Zimmermann H (2014) NTPDase2 and purinergic signaling control progenitor cells proliferation in neurogenic niches of the adult mouse brain. Stem Cells. doi: 10.1002/stem.1846 Google Scholar
  14. 14.
    Massé K, Bhamra S, Eason R, Dale N, Jones EA (2007) Purine-mediated signalling triggers eye development. Nature 449:1058–1062CrossRefPubMedGoogle Scholar
  15. 15.
    Massé K, Eason R, Bhamra S, Dale N, Jones EA (2006) Comparative genomic and expression analysis of the conserved NTPDase gene family in Xenopus. Genomics 87:366–381CrossRefPubMedGoogle Scholar
  16. 16.
    Cheng AWM, Kong LW, Tung EKK, Siow NL, Choi RCY, Zhu SQ, Peng BH, Tsim KWK (2003) cDNA encodes Xenopus P2Y1 nucleotide receptor: Expression at the neuromuscular junctions. Neuroreport 14:351–357CrossRefPubMedGoogle Scholar
  17. 17.
    Léon C, Hechler B, Freund M, Eckly A, Vial C, Ohlmann P, Dierich A, LeMeur M, Cazenave JP, Gachet C (1999) Defective platelet aggregation and increased resistance to thrombosis in purinergic P2Y1 receptor-null mice. J Clin Invest 104:1731–1737CrossRefPubMedCentralPubMedGoogle Scholar
  18. 18.
    Laplante MA, Monassier L, Freund M, Bousquet P, Gachet C (2010) The purinergic P2Y1 receptor supports leptin secretion in adipose tissue. Endocrinology 151:2060–2070CrossRefPubMedGoogle Scholar
  19. 19.
    Haverkamp S, Wässle H (2000) Immunocytochemical analysis of the mouse retina. J Comp Neurol 424:1–23CrossRefPubMedGoogle Scholar
  20. 20.
    tom Dieck S, Altrock WD, Kessels MM, Qualmann B, Regus H, Brauner D, Fejtová A, Bracko O, Gundelfinger ED, Brandstätter JH (2005) Molecular dissection of the photoreceptor ribbon synapse: Physical interaction of Bassoon and RIBEYE is essential for the assembly of the ribbon complex. J Cell Biol 168:825–836CrossRefPubMedCentralPubMedGoogle Scholar
  21. 21.
    Wässle H, Puller C, Müller F, Haverkamp S (2009) Cone contacts, mosaics, and territories of bipolar cells in the mouse retina. J Neurosci 29:106–117CrossRefPubMedGoogle Scholar
  22. 22.
    Chow RL, Lang RA (2001) Early eye development in vertebrates. Annu Rev Cell Dev Biol 17:255–296CrossRefPubMedGoogle Scholar
  23. 23.
    Sinn R, Wittbrodt J (2013) An eye on eye development. Mech Dev 130:347–358CrossRefPubMedGoogle Scholar
  24. 24.
    Sanderson J, Dartt DA, Trinkaus-Randall V, Pintor J, Civan MM, Delamere NA, Fletcher EL, Salt TE, Grosche A, Mitchell CH (2014) Purines in the eye: Recent evidence for the physiological and pathological role of purines in the RPE, retinal neurons, astrocytes, Müller cells, lens, trabecular meshwork, cornea and lacrimal gland. Exp Eye Res 127:270–279CrossRefPubMedGoogle Scholar
  25. 25.
    Wurm A, Erdmann I, Bringmann A, Reichenbach A, Pannicke T (2009) Expression and function of P2Y receptors on Müller cells of the postnatal rat retina. Glia 57:1680–1690CrossRefPubMedGoogle Scholar
  26. 26.
    Dilip R, Ishii T, Imada H, Wada-Kiyama Y, Kiyama R, Miyachi E, Kaneda M (2013) Distribution and development of P2Y1-purinoceptors in the mouse retina. J Mol Histol 44:639–644CrossRefPubMedGoogle Scholar
  27. 27.
    Sugioka M, Zhou WL, Hofmann HD, Yamashita M (1999) Involvement of P2 purinoceptors in the regulation of DNA synthesis in the neural retina of chick embryo. Int J Dev Neurosci 17:135–144CrossRefPubMedGoogle Scholar
  28. 28.
    Pearson RA, Dale N, Llaudet E, Mobbs P (2005) ATP released via gap junction hemichannels from the pigment epithelium regulates neural retinal progenitor proliferation. Neuron 46:731–744CrossRefPubMedGoogle Scholar
  29. 29.
    Sholl-Franco A, Fragel-Madeira L, Macama AC, Linden R (2010) Ventura AL (2010) ATP controls cell cycle and induces proliferation in the mouse developing retina. Int J Dev Neurosci 28:63–73CrossRefPubMedGoogle Scholar
  30. 30.
    Iandiev I, Wurm A, Pannicke T, Wiedemann P, Reichenbach A, Robson SC, Zimmermann H, Bringmann A (2007) Ectonucleotidases in Müller glial cells of the rodent retina: Involvement in inhibition of osmotic cell swelling. Purinergic Signal 3:423–433CrossRefPubMedCentralPubMedGoogle Scholar
  31. 31.
    Ricatti MJ, Alfie LD, Lavoie EG, Sévigny J, Schwarzbaum PJ, Faillace MP (2009) Immunocytochemical localization of NTPDases1 and 2 in the neural retina of mouse and zebrafish. Synapse 63:291–307CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Kristine Gampe
    • 1
    Email author
  • Silke Haverkamp
    • 2
  • Simon C. Robson
    • 3
  • Christian Gachet
    • 4
  • Laura Hüser
    • 2
  • Amparo Acker-Palmer
    • 1
    • 5
  • Herbert Zimmermann
    • 1
  1. 1.Institute of Cell Biology and NeuroscienceGoethe-UniversityFrankfurt am MainGermany
  2. 2.Max-Planck-Institute for Brain ResearchFrankfurt am MainGermany
  3. 3.Department of Medicine, Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonUSA
  4. 4.EFS-AlsaceINSERM, Université de StrasbourgStrasbourgFrance
  5. 5.Focus Program Translational Neurosciences (FTN)University of MainzMainzGermany

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