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The Role of Quaking in Mammalian Embryonic Development

  • Chapter
Post-Transcriptional Regulation by STAR Proteins

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 693))

Abstract

Functional studies of the mouse quaking gene (Qk) have focused on its role in the postnatal central nervous system during myelination. However, the death of the majority of homozygous mouse quaking alleles revealed that quaking has a critical role in embryonic development prior to the start of myelination. Surprisingly, the lethal alleles revealed that quaking has a function in embryonic blood vessel formation and remodeling. Further studies of the extraembryonic yolk sac showed that Qk regulates visceral endoderm differentiated function at the cellular level, including the local synthesis of retinoic acid (RA), which then exerts paracrine control of endothelial cells within adjacent mesoderm. Endoderm-derived RA regulates proliferation of endothelial cells and extracellular matrix (ECM) production, which in a reciprocal manner, modulates visceral endoderm survival and function. Although exogenous RA can rescue endothelial cell growth control and ECM production in mutants carrying a lethal mutation, which lack functional Qk, neither visceral endoderm function nor vascular remodeling is restored. Thus, Qk also regulates cell autonomous functions of visceral endoderm that are critical for vascular remodeling. Interestingly, quaking is highly expressed during normal cardiac development, particularly in the outflow tract, suggesting potentially unique functions in the developing heart. Together, the work on Qk in mammalian embryos reveals an essential, yet under appreciated, role in cardiovascular development. This suggests that certain functions may remain conserved in the early embryo throughout the evolution of nonvertebrate and vertebrate organisms and that additional roles for quaking remain to be discovered.

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References

  1. Bohnsack BL, Lai L, Northrop JL et al. Visceral endoderm function is regulated by quaking and required for vascular development. Genesis 2006;44(2):93–104.

    Article  PubMed  Google Scholar 

  2. Noveroske JK, Lai L, Gaussin V et al. Quaking is essential for blood vessel development. Genesis 2002;32(3):218–230.

    Article  CAS  PubMed  Google Scholar 

  3. Kondo T, Furuta T, Mitsunaga K et al. Genomic organization and expression analysis of the mouse qkI locus. Mamm Genome 1999;10:662–669.

    Article  CAS  PubMed  Google Scholar 

  4. Wu J, Zhou L, Tonissen K et al. The STAR protein quakingI-5 (QKI-5) has a novel nuclear localization signal and shuttles between the nucleus and the cytoplasm. J Biol Chem 1999;274(41):29202–29210.

    Article  CAS  PubMed  Google Scholar 

  5. Wu JI, Reed RB, Grabowski PJ et al. Function of quaking in myelination: regulation of alternative splicing. Proc Natl Acad Sci USA 2002;99(7):4233–4238.

    Article  CAS  PubMed  Google Scholar 

  6. Hardy RJ, Loushin CL, Friedrich VL Jr et al. Glial cell type-specific expression of QKI proteins is altered in quaking viable mutant mice. J Neurosci 1996;16(24):7941–7949.

    CAS  PubMed  Google Scholar 

  7. Zhao L, Tian D, Xia M et al. Rescuing qkV dysmyelination by a single isoform of the selective RNA-binding protein QKI. J Neurosci 2006;26(44):11278–11286.

    Article  CAS  PubMed  Google Scholar 

  8. Ebersole TA, Rho O, Artz K. The proximal end of mouse chromosome 17: New molecular markers identify a deletion associated with quaking viable. Genetics 1992;131:183–190.

    CAS  PubMed  Google Scholar 

  9. Lorenzetti DL, Antalffy B, Vogel H et al. The neurological mutant quakingviable is Parkin deficient. Mamm Genome 2004;15:210–217.

    Article  CAS  PubMed  Google Scholar 

  10. Lorenzetti DL, Bishop C, Justice MJ. Deletion of the Parkin co-regulated gene causes male sterility in the quakingviable mouse mutant. Proc Natl Acad Sci USA 2004;101:8402–8407.

    Article  CAS  PubMed  Google Scholar 

  11. Cox RD, Hugill A, Shedlovsky A et al. Contrasting effects of ENU-induced embryonic lethal mutations of the quaking gene. Genomics 1999;57:333–341.

    Article  CAS  PubMed  Google Scholar 

  12. Justice MJ, Bode VC. Three ENU-induced alleles of the murine quaking locus are recessive embryonic lethal mutations. Genet Res 1988;51:95–102.

    Article  CAS  PubMed  Google Scholar 

  13. Li Z, Takakura N, Oike Y et al. Defective smooth muscle development in qkI-deficient mice. Development, Growth and Differentiation 2003;45(5–6):449–462.

    Article  CAS  PubMed  Google Scholar 

  14. Chen T, Richard S. Structure-function analysis of qkI: a lethal point mutation in mouse quaking prevents homodimerization. Mol Cell Biol 1998;18(8):4863–4871.

    CAS  PubMed  Google Scholar 

  15. Shedlovsky A, King TR, Dove WF. Saturation germ line mutagenesis of the murine t region including a lethal allele at the quaking locus. Proc Natl Acad Sci USA 1988;85:180–184.

    Article  CAS  PubMed  Google Scholar 

  16. Tam PP, Behringer RR. Mouse gastrulation: the formation of a mammalian body plan. Mech Dev 1997;68(1–2):3–25.

    Article  CAS  PubMed  Google Scholar 

  17. Flamme I, Frolich T, Risau W. Molecular mechanisms of vasculogenesis and embryonic angiogenesis. J Cell Physiol 1997;173(2):206–210.

    Article  CAS  PubMed  Google Scholar 

  18. Noden DM. Embryonic origins and assembly of blood vessels. Am Rev Respir Dis 1989;140(4):1097–1103.

    CAS  PubMed  Google Scholar 

  19. Hopper AF, Heart NH. Foundations of animal development. New York: Oxford University Press; 1985.

    Google Scholar 

  20. Lucitti JL, Jones EA, Huang C et al. Vascular remodeling of the mouse yolk sac requires hemodynamic force. Development. 2007 Sep;134(18):3317–3326.

    Article  CAS  PubMed  Google Scholar 

  21. Ryder SP, Williamson JR. Specificity of the STAR/GSG domain protein Qk1: implications for the regulation of myelination. RNA. 2004 Sep;10(9):1449–1458.

    Article  CAS  PubMed  Google Scholar 

  22. Saccomanno L, Loushin C, Jan E et al. The STAR protein QKI-6 is a translational repressor. Proc Natl Acad Sci USA 1999;96(22):12605–12610.

    Article  CAS  PubMed  Google Scholar 

  23. Ryder SP, Frater LA, Abramovitz DL et al. RNA target specificity of the STAR/GSG domain post-transcriptional regulatory protein GLD-1. Nat Struct Mol Biol 2004;11(1):20–28.

    Article  CAS  PubMed  Google Scholar 

  24. Jan E, Motzny CK, Graves LE et al. The STAR protein, GLD-1, is a translational regulator of sexual identity in Caenorhabditis elegans. EMBO J 1999;18(1):258–269.

    Article  CAS  PubMed  Google Scholar 

  25. Risua W. Mechanisms of angiogenesis. Nature 1997;386:671–674.

    Article  Google Scholar 

  26. Carmeliet P. Blood vessels and nerves: common signals, pathways and diseases. Nat Rev 2003;4(9):710–720.

    Article  CAS  Google Scholar 

  27. Carmeliet P, Collen D. Transgenic mouse models in angiogenesis and cardiovascular disease. J Pathol 2000;190(3):387–405.

    Article  CAS  PubMed  Google Scholar 

  28. Becker S, Wang ZJ, Massey H et al. A role for Indian hedgehog in extraembryonic endoderm differentiation in F9 cells and the early mouse embryo. Dev Biol 1997;187(2):298–310.

    Article  CAS  PubMed  Google Scholar 

  29. Dyer MA, Farrington SM, Mohn D et al. Indian hedgehog activates hematopoiesis and vasculogenesis and can respecify prospective neurectodermal cell fate in the mouse embryo. Development (Cambridge, England) 2001;128(10):1717–1730.

    CAS  Google Scholar 

  30. Carmeliet P, Ferreira V, Breier G et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 1996;380(6573):435–439.

    Article  CAS  PubMed  Google Scholar 

  31. Ferrara N, Carver-Moore K, Chen H et al. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 1996;380:349–442.

    Article  Google Scholar 

  32. Leconte I, Fox JC, Baldwin HS et al. Adenoviral-mediated expression of antisense RNA to fibroblast growth factors disrupts murine vascular development. Dev Dyn 1998;213(4):421–430.

    Article  CAS  PubMed  Google Scholar 

  33. Lee SH, Schloss DJ, Swain JL. Maintenance of vascular integrity in the embryo requires signaling through the fibroblast growth factor receptor. The J Biol Chem 2000;275(43):33679–33687.

    Article  CAS  Google Scholar 

  34. Maye P, Becker S, Kasameyer E et al. Indian hedgehog signaling in extraembryonic endoderm and ectoderm differentiation in ES embryoid bodies. Mech Dev 2000;94(1–2):117–132.

    Article  CAS  PubMed  Google Scholar 

  35. Shalaby F, Ho J, Stanford WL et al. A requirement for Flk1 in primitive and definitive hematopoiesis and vasculogenesis. Cell 1997;89(6):981–990.

    Article  CAS  PubMed  Google Scholar 

  36. Shalaby F, Rossant J, Yamaguchi TP et al. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 1995;376(6535):62–66.

    Article  CAS  PubMed  Google Scholar 

  37. Shing Y, Folkman J, Sullivan R et al. Heparin affinity: purification of a tumor-derived capillary endothelial cell growth factor. Science (New York, NY 1984;223(4642):1296–1299.

    Article  CAS  Google Scholar 

  38. Patan S. Vasculogenesis and angiogenesis as mechanisms of vascular network formation, growth and remodeling. Journal of Neuro-Oncology 2000;50(1–2):1–15.

    Article  CAS  PubMed  Google Scholar 

  39. Baron MH. Embryonic origins of mammalian hematopoiesis. Exp Hematol 2003;31(12):1160–1169.

    Article  CAS  PubMed  Google Scholar 

  40. Winnier G, Blessing M, Labosky PA et al. Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev 1995;9(17):2105–2116.

    Article  CAS  PubMed  Google Scholar 

  41. Lai L, Bohnsack BL, Niederreither K et al. Retinoic acid regulates endothelial cell proliferation during vasculogenesis. Development (Cambridge, England) 2003;130(26):6465–6474.

    CAS  Google Scholar 

  42. Bohnsack BL, Lai L, Dolle P et al. Signaling hierarchy downstream of retinoic acid that independently regulates vascular remodeling and endothelial cell proliferation. Genes Dev 2004;18(11):1345–1358.

    Article  CAS  PubMed  Google Scholar 

  43. Dumont DJ, Gradwohl G, Fong GH et al. Dominant-negative and targeted null mutations in the endothelial receptor tyrosine kinase, tek, reveal a critical role in vasculogenesis of the embryo. Genes Dev 1994;8(16):1897–1909.

    Article  CAS  PubMed  Google Scholar 

  44. Suri C, Jones PF, Patan S et al. Requisite role of angiopoietin-1, a ligand for the tie2 receptor, during embryonic angiogenesis. Cell 1996;87:1171–1180.

    Article  CAS  PubMed  Google Scholar 

  45. Lindahl P, Johansson BR, Leveen P et al. Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science (New York, NY 1997;277(5323):242–245.

    Article  CAS  Google Scholar 

  46. Hirschi KK, Rohovsky SA, Beck LH et al. Endothelial cells modulate the proliferation of mural cell precursors via platelet-derived growth factor-BB and heterotypic cell contact. Circ Res 1999;84(3):298–305.

    CAS  PubMed  Google Scholar 

  47. Hirschi KK, Rohovsky SA, D’Amore PA. PDGF, TGF-beta and heterotypic cell-cell interactions mediate endothelial cell-induced recruitment of 10T1/2 cells and their differentiation to a smooth muscle fate. J Cell Biol 1998;141(3):805–814.

    Article  CAS  PubMed  Google Scholar 

  48. Hirschi KK, Burt JM, Hirschi KD et al. Gap junction communication mediates transforming growth factor-beta activation and endothelial-induced mural cell differentiation. Circ Res 2003;93(5):429–437.

    Article  CAS  PubMed  Google Scholar 

  49. Limbourg FP, Takeshita K, Radtke F et al. Essential role of endothelial Notch1 in angiogenesis. Circulation 2005;111(14):1826–1832.

    Article  CAS  PubMed  Google Scholar 

  50. Kwon SM, Eguchi M, Wada M et al. Specific Jagged-1 signal from bone marrow microenvironment is required for endothelial progenitor cell development for neovascularization. Circulation 2008;118(2):157–165.

    Article  PubMed  Google Scholar 

  51. Fischer A, Schumacher N, Maier M et al. The Notch target genes Hey1 and Hey2 are required for embryonic vascular development. Genes Dev 2004;18(8):901–911.

    Article  CAS  PubMed  Google Scholar 

  52. Bohnsack BL, Hirschi KK. Red light, green light: signals that control endothelial cell proliferation during embryonic vascular development. Cell Cycle (Georgetown, Tex 2004;3(12):1506–1511.

    CAS  Google Scholar 

  53. Byrd N, Becker S, Maye P et al. Hedgehog is required for murine yolk sac angiogenesis. Development 2002 Jan;129(2):361–372.

    CAS  PubMed  Google Scholar 

  54. Dickson MC, Martin JS, Cousins FM et al. Defective haematopoiesis and vasculogenesis in transforming growth factor-beta 1 knock out mice. Development (Cambridge, England) 1995;121(6):1845–1854.

    CAS  Google Scholar 

  55. Goumans MJ, Zwijsen A, van Rooijen MA et al. Transforming growth factor-beta signalling in extraembryonic mesoderm is required for yolk sac vasculogenesis in mice. Development (Cambridge, England) 1999;126(16):3473–3483.

    CAS  Google Scholar 

  56. Larsson J, Goumans MJ, Sjostrand LJ et al. Abnormal angiogenesis but intact hematopoietic potential in TGF-beta type I receptor-deficient mice. EMBO J 2001;20(7):1663–1673.

    Article  CAS  PubMed  Google Scholar 

  57. Barsi JC, Rajendra R, Wu JI et al. Mind bomb1 is a ubiquitin ligase essential for mouse embryonic development and Notch signaling. Mech Dev 2005;122(10):1106–1117.

    Article  CAS  PubMed  Google Scholar 

  58. Enciso JM, Hirschi KK. Nutrient regulation of tumor and vascular endothelial cell proliferation. Curr Cancer Drug Targets 2007;7(5):432–437.

    Article  CAS  PubMed  Google Scholar 

  59. Ebersole TA, Chen Q, Justice MJ et al. The quaking gene product necessary in embryogenesis and myelination combines features of RNA binding and signal transduction proteins. Nat Genet 1996;12:260–265.

    Article  CAS  PubMed  Google Scholar 

  60. Hardy RJ. QKI expression is regulated during neuron-glial cell fate decisions. J Neurosci Res 1998;54:46–57.

    Article  CAS  PubMed  Google Scholar 

  61. Hardy RJ. The QkI Gene. In: Lazzarini R, ed. Myelin Biology and Disorders. Vol I. Philadelphia: Elsevier Science; 2004:643–659.

    Chapter  Google Scholar 

  62. Zorn AM, Krieg PA. The KH domain protein encoded by quaking functions as a dimer and is essential for notochord development in Xenopus embryos. Genes Dev 1997;11:2176–2190.

    Article  CAS  PubMed  Google Scholar 

  63. Zorn AM, Grow M, Patterson KD et al. Remarkable sequence conservation of transcripts encoding amphibian and mammalian homologues of quaking, a KH domain RNA-binding protein. Gene 1997;188:199–206.

    Article  CAS  PubMed  Google Scholar 

  64. Zaffran S, Astier M, Gratecos D et al. The held out wings (how) Drosophila gene encodes a putative RNA-binding protein involved in the control of muscular and cardiac activity. Development 1997;124:2087–2098.

    CAS  PubMed  Google Scholar 

  65. Tanaka H, Abe K, Kim C. Cloning and expression of the quaking gene in zebrafish embryo. Mech Dev 1997;69:209–213.

    Article  CAS  PubMed  Google Scholar 

  66. Volk T, Israeli D, Nir R et al. Tissue development and RNA control: “HOW”is it coordinated? Trends Genet 2008;24(2):94–101.

    Article  CAS  PubMed  Google Scholar 

  67. Zacchigna S, Ruiz de Almodovar C, Carmeliet P. Similarities between angiogenesis and neural development: what small animal models can tell us. Current Topics in Dev Biol 2008;80:1–55.

    Article  Google Scholar 

  68. Carmeliet P, Tessier-Lavigne M. Common mechanisms of nerve and blood vessel wiring. Nature 2005;436(7048):193–200.

    Article  CAS  PubMed  Google Scholar 

  69. Sondell M, Sundler F, Kanje M. Vascular endothelial growth factor is a neurotrophic factor which stimulates axonal outgrowth through the flk-1 receptor. Eur J Neurosci 2000;12(12):4243–4254.

    Article  CAS  PubMed  Google Scholar 

  70. Shima DT, Mailhos C. Vascular Dev Biol: getting nervous. Curr Opin Genet Dev 2000;10(5):536–542.

    Article  CAS  PubMed  Google Scholar 

  71. Hartenstein V, Mandal L. The blood/vascular system in a phylogenetic perspective. Bioessays 2006;28(12):1203–1210.

    Article  PubMed  Google Scholar 

  72. Medioni C, Astier M, Zmojdzian M et al. Genetic control of cell morphogenesis during Drosophila melanogaster cardiac tube formation. J Cell Biol 2008;182(2):249–261.

    Article  CAS  PubMed  Google Scholar 

  73. Legg JA, Herbert JM, Clissold P et al. Slits and Roundabouts in cancer, tumour angiogenesis and endothelial cell migration. Angiogenesis 2008;11(1):13–21.

    Article  PubMed  Google Scholar 

  74. Helenius IT, Beitel GJ. The first “Slit” is the deepest: the secret to a hollow heart. J Cell Biol 2008;182(2):221–223.

    Article  CAS  PubMed  Google Scholar 

  75. Killeen MT, Sybingco SS. Netrin, Slit and Wnt receptors allow axons to choose the axis of migration. Dev Biol 2008;323(2):143–151.

    Article  CAS  PubMed  Google Scholar 

  76. Noveroske JK, Hardy R, Dapper J et al. A new ENU-Induced allele of the mouse quaking gene causes severe central nervous system dysmyelination. Mamm Genome 2005;16:672–682.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Departments of Molecular and Human Genetics and Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza MS227, R804, Houston, Texas, 77030, USA

    Monica J. Justice & Karen K. Hirschi

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  1. Monica J. Justice
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  2. Karen K. Hirschi
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Correspondence to Monica J. Justice .

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Editors and Affiliations

  1. Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel

    Talila Volk BSc, MSc, PhD

  2. Department of Molecular Genetics and Microbiology, Institute of Cell and Molecular Biology, University of Texas at Austin, Austin, Texas, USA

    Karen Artzt BA, PhD

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Justice, M.J., Hirschi, K.K. (2010). The Role of Quaking in Mammalian Embryonic Development. In: Volk, T., Artzt, K. (eds) Post-Transcriptional Regulation by STAR Proteins. Advances in Experimental Medicine and Biology, vol 693. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-7005-3_6

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