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New Strategies in Developmental Biology: In vivo Mutagenesis as a Tool to Dissect Mammalian Development

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Book cover Vectors as Tools for the Study of Normal and Abnormal Growth and Differentiation

Part of the book series: NATO ASI Series ((ASIH,volume 34))

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Abstract

Just over 100 years ago, Roux published an experiment, in which one blastomere of a two cell embryo was destroyed (Roux, 1888). Roux did this experiment to test the, at that time controversial, hypothesis whether development is strictly mosaic and predetermined or whether it is influenced by its environment. Roux recognized that the natural laws underlying the formative processes of development could only be elicited and analyzed by experimentation. Thus, he transformed embryology from a descriptive into an experimental discipline he termed Entwicklungsmechanik (developmental mechanics). Roux noted in his introduction to the new journal Archiv für Entwicklungsmechanik der Organismen (1894): “The extremely diverse structures of multicellular organisms may be traced back to the few modi operandi of cell growth, of cell evanescence, cell division, cell migration, active cell formation, cell elimination, and the qualitative metamorphosis of cells”.

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References

  • Awgulewitsch A, Utset MF, Hart CP, McGinnis W, Ruddle FH (1986) Spatial restriction in expression of a mouse homeobox locus within the central nervous system. Nature 320: 328–335

    Article  PubMed  CAS  Google Scholar 

  • Balling R, Deutsch U, Gruss P (1988) Undulated, a mutation affecting the development of the mouse skeleton, has a point mutation in the paired box of pax 1. Cell 55: 531–535

    Google Scholar 

  • Behringer RR, Mathews LS, Palmiter RD, Brinster RL (1988) Dwarf mice produced by genetic ablation of growth hormone-expressing cells. Genes Dev 2: 453–461

    Article  PubMed  CAS  Google Scholar 

  • Bell RM (1986) Protein kinase C activation by diacylglycerol second messengers. Cell 45: 631–632

    Article  PubMed  CAS  Google Scholar 

  • Bopp D, Burn M, Baumgartner S, Frigerio G, Noll M (1986) Conservation of a large protein domain in the segmentation gene paired and in functionally related genes of Drosophila. Cell 47: 1033–1040

    Article  PubMed  CAS  Google Scholar 

  • Bradley A, Evans M, Kaufmann MH, Robertson E (1984) Formation of germline chimeras from embryo-derived teratocarcinoma cell lines. Nature 309, 255–256

    Article  PubMed  CAS  Google Scholar 

  • Breier G, Dressler GR, Gruss P (1988) Primary structure and developmental expression pattern of hox 3.1, a member of the murine hox 3 homeo box gene cluster. EMBO J 7: 1329–1336

    PubMed  CAS  Google Scholar 

  • Bürglin TR, Wright CVE, Robertis E (1987) Translational control in homeo box mRNAs? Nature 330: 701–702

    Article  PubMed  Google Scholar 

  • Capecchi MR (1980) High efficiency transformation by direct microinjection of DNA into cultured mammalian cells. Cell 22: 479–488

    Article  PubMed  CAS  Google Scholar 

  • Chavrier P, Zerial M, Lemaire P, Almendrai J, Bravo R, Charney P (1988) A gene encoding a protein with zink fingers is activated during G0/G1 transition in cultured cells. EMBO J 7: 29–35

    PubMed  CAS  Google Scholar 

  • Chowdhury K, Deutsch U, Gruss P (1987) A multigene family encoding several “finger” structures is present and differentially active in mammalian genomes. Cell 48: 771 – 778

    Article  PubMed  CAS  Google Scholar 

  • Chowdhury K, Dressler GR, Breier G, Deutsch U, Gruss P (1988a) The primary structure of the murine multifinger gene mkr2 and its specific expression in developing and adult neurons. EMBO J 7: 1345–1353

    PubMed  CAS  Google Scholar 

  • Chowdhury K, Rohdewohld H, Gruss P (1988b) Specific and ubiquitous expression of different Zn finger protein genes in the mouse. Nucl Acids Res 16: 9995–10011

    Article  PubMed  CAS  Google Scholar 

  • Colberg-Poley AM, Voss SD, Chowdhury K, Stewart CL, Wagner EF, Gruss P (1985) Clustered homeo boxes are differentially expressed during murine development. Cell 43: 39–45

    Article  PubMed  CAS  Google Scholar 

  • Côté S, Preiss A, Haller J, Schuh R, Kienlin A, Scifert E, Jäckle H (1987) The goose berry-zipper region of Drosophila: five genes encode different spatially restricted transcripts in the embryo. EMBO J 6: 2793–2801

    PubMed  Google Scholar 

  • Davis CA, Rossant J, Joyner AL (1988) Expression of the homeo box-containing gene en-2 delineates a specific region of the developing mouse brain. Genes Dev 2: 361–371

    Article  PubMed  CAS  Google Scholar 

  • Deutsch U, Dressler GR, Gruss P (1988) Pax 1, a member of a paired box homologous murine family, is expressed in segmented structures during development. Cell 53: 617–625

    Article  PubMed  CAS  Google Scholar 

  • Dony C, Gruss P (1987) Specific expression of the hox-1.3 homeo box gene in murine embryonic structures originating from or induced by the mesoderm. EMBO J 6: 2965–2975

    PubMed  CAS  Google Scholar 

  • Dressler GR, Gruss P (1988) Do multigene families regulate vertebrate development? TIG 4: 214–218

    Article  PubMed  CAS  Google Scholar 

  • Dressler GR, Deutsch U, Balling R, Simon D, Guenet J-L, Gruss P (1988) Murine genes with homology to Drosophila segmentation genes. Development 104 Supplement: 181–186

    Google Scholar 

  • Driever W, Nüsslein-Volhard C (1988) A gradient of bicoid protein in Drosophila embryos. Cell 54: 83–93

    Article  PubMed  CAS  Google Scholar 

  • Duprey P, Chowdhury K, Dressler GR, Balling R, Simon D, Guenet J-L, Gruss P (1988) A mouse gene homologous to the Drosophila gene caudal is expressed in epithelial cells from the embryonic intestine. Genes Dev 2: 1647–1654

    Article  PubMed  CAS  Google Scholar 

  • Evans MJ, Kaufmann MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292: 154–165

    Article  PubMed  CAS  Google Scholar 

  • Fainsod A, Awgulewitsch A, Ruddle FH (1987) Expression of the murine homeo box gene hox-1.5 during embryogenesis. Dev Biol 124: 125–133

    Article  PubMed  CAS  Google Scholar 

  • Fienberg AA, Utset MF, Bogarad LD, Hart CP, Awgulewitsch A, Ferguson-Smith A, Fainsod A, Rabin M, Ruddle FH (1987) Homeobox genes in murine development. Curr Top Dev Biol 23: 233–256

    Article  PubMed  CAS  Google Scholar 

  • Finney M, Ruvkun G, Horvitz HR (1988) The C. elegans cell lineage and differentiation gene unc-86 encodes a protein with a homeodomain and extended similarity to transcription factors. Cell 55: 757–769

    Article  PubMed  CAS  Google Scholar 

  • Frigerio G, Burri M, Bopp D, Baumgartner S, Noll M (1986) Structure of the segmentation gene paired and the Drosophila PRD gene set as part of a gene network. Cell 47: 735–746

    Article  PubMed  CAS  Google Scholar 

  • Gaunt SJ (1987) Homeo box gene hox-1.5 expression in mouse embryos: earliest detection by in situ hybridization is during gastrulation. Development 101: 51–61

    PubMed  CAS  Google Scholar 

  • Gaunt SJ (1988) Mouse homeo box gene transcripts occupy different but overlapping domains in embryonic germ layers and organs: a comparison of hox-3.1 and hox1.5. Development 103: 135–144

    PubMed  CAS  Google Scholar 

  • Gaunt SJ, Sharpe PT, Duboule D (1988) Spatially restricted domains of homeo-gene transcripts in mouse embryos: relation to a segmented body plan. Development 104 Supplement: 169–179

    Google Scholar 

  • Gehring WJ, Hiromi Y (1986) Homeotic genes and the homeobox. Ann Rev Genet 20: 147–173

    Article  PubMed  CAS  Google Scholar 

  • Gossler A, Doetschmann T, Korn R, Serfling E, Kemler R (1986) Transgenesis by means of blastocyst-derived embryonic stem cell lines. Proc Natl Acad Sci USA 83: 9065–9069

    Article  PubMed  CAS  Google Scholar 

  • Hatzopoulos AK, Schlokat U, Gruss P (1988) Enhancers and other cis-acting regulatory sequences. In: Hames BD, Glover DM (eds) Frontiers in molecular biology: Transcription and splicing. IRL Press, Oxford Washington DC, p 43

    Google Scholar 

  • Heberlein U, Tjian R (1988) Temporal pattern of alcohol dehydrogenase gene transcription reproduced by Drosophila stage-specific embryo extracts. Nature 331: 410–415

    Article  PubMed  CAS  Google Scholar 

  • Herr W, Sturm RA, Clerc RG, Corcoran LM, Baltimore D, Sharp PA, Ingraham HA, Rosenfeld MG, Finney M, Ruvkun G, Horvitz RH (1988) The POU domain: a large conserved region in the mammalian pit-1, oct-1, oct-2, and Caenor-habditiselegans unc-86 gene products. Genes Dev 2: 1513–1516

    Article  PubMed  CAS  Google Scholar 

  • Herskowitz I (1987) Functional inactivation of genes by dominant negative mutations. Nature 329: 219–222

    Article  PubMed  CAS  Google Scholar 

  • Holland PWH, Hogan BLM (1988a) Spatially restricted patterns of expression of the mouse homeobox-containing gene hox-2.1 during mouse embryogenesis. Development 102:159–174 Holland PWH, Hogan BLM (1988b) Expression of homeobox genes during mouse development: a review. Genes Dev 2:773–782 Hooper M, Hardy K, Handyside A, Hunter S, Monk M (1987) Hprt-deficient (Lesch-Nyhan) mouse embryos derived from germline colonization by cultured cells. Nature 326:292–295

    Google Scholar 

  • Ingham PW (1988) The molecular genetics of embryonic pattern formation in Drosophila. Nature 335: 25–34

    Article  PubMed  CAS  Google Scholar 

  • Ingraham HA, Chen R, Mangalam HJ, Elsholtz HP, Flynn SE, Lin CR, Simmons DM, Swanson L, Rosenfeld MG (1988) A tissue specific transcription factor containing a homeo domain specifies a pituitary phenotype. Cell 55: 519–529

    Article  PubMed  CAS  Google Scholar 

  • Jackson IJ, Schofield P, Hogan BLM (1985) A mouse homeobox gene is expressed during embryogenesis and in adult kidney. Nature 317: 745–748

    Article  PubMed  CAS  Google Scholar 

  • Jaenisch R (1988) Transgenic animals. Science 240: 1468–1474

    Article  PubMed  CAS  Google Scholar 

  • Joyner AL, Martin GR (1987) En-1 and en-2. two mouse genes with sequence homology to the Drosophila engrailed gene: expression during embryogenesis. Genes Dev 1: 29–38

    Google Scholar 

  • Joyner AL, Kornberg T, Coleman KG, Cox DR, Martin GR (1985) Expression during embryogenesis of a mouse gene with sequence homology to the Drosophila engrailed gene. Cell 43: 29–37

    Article  PubMed  CAS  Google Scholar 

  • Katsuki M, Sato M, Kimura M, Yokoyama M, Kobayashi K, Nomura T (1988) Conver-sion of normal behavior to Shiverer by myelin basic protein antisense cDNA in transgenic mice. Science 242: 593–595

    Article  Google Scholar 

  • Kessel M, Gruss P (1988) Open reading frames and translational control. Nature 332: 117–118

    Article  PubMed  CAS  Google Scholar 

  • Kessel M, Schulze F, Fibi M, Gruss P (1987a) Primary structure and nuclear localization of a murine homeo domain protein. Proc Natl Acad Sci USA 84: 5306–5310

    Article  PubMed  CAS  Google Scholar 

  • Kessel M, Fibi M, Gruss P (1987b) Organization of homeodomain proteins. In: Sato GH, Harris SE (eds) Cellular factors of development and differentiation-embryos, teratocarcinomas and differentiated tissues. Alan Liss, New York, p 93

    Google Scholar 

  • Kilchherr F, Baumgartner S, Bopp D, Frei E, Noll M (1986) Isolation of the paired gene of Drosophila and its spatial expression during early embryogenesis. Nature 321: 493–499

    Article  CAS  Google Scholar 

  • Kuehn MR, Bradley A, Robertson EJ, Evans MJ (1987) A potential animal model for Lesch-Nyhan syndrome through introduction of hprt mutations into mice. Nature 326: 295–298

    Article  PubMed  CAS  Google Scholar 

  • Landel CP, Zhao J, Bok D, Evans GA (1988) Lens-specific expression of recombinant ricin induces developmental defects in the eyes of transgenic mice. Genes Dev 2: 1168 – 1178

    Article  PubMed  CAS  Google Scholar 

  • LeMouellic H, Condamine H, Brulet P (1988) Pattern of transcription of the homeo-gene hox-3.1 in the mouse embryo. Genes Dev 2: 125–135

    Article  CAS  Google Scholar 

  • Lewis EB (1978) A gene complex controlling segmentation in Drosophila. Nature 276: 565–570

    Article  PubMed  CAS  Google Scholar 

  • Macdonald PM, Ingham P, Struhl G (1986) Isolation, structure, and expression of even-skipped: a second pair rule gene of Drosophila containing a homeobox. Cell 47: 721–734

    Article  PubMed  CAS  Google Scholar 

  • Mahon KA, Westphal H, Gruss P (1988) Expression of homeobox gene hox 1.1 during mouse embryogenesis. Development 104 Supplement: 187–195

    Google Scholar 

  • Mansour SL, Thomas KR, Capecchi MR (1988) Dispurtion of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes. Nature 336: 348–352

    Article  PubMed  CAS  Google Scholar 

  • Martin GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA 78: 7634–7638

    Article  PubMed  CAS  Google Scholar 

  • McGinnis W, Levine MS, Hafen E, Kuroiwa A, Gehring W (1984a) A conserved DNA sequence in homeotic genes of the Drosophila melanogaster Antennapedia and bithorax complexes. Nature 308: 428–433

    Article  PubMed  CAS  Google Scholar 

  • McGinnis W, Garber RL, Wirz J, Kuroiwa A, Gehring WJ (1984b) A homologous protein coding sequence in Drosophila homeotic genes and its conservation in other metazoans. Cell 38: 403–409

    Article  Google Scholar 

  • Miller J, McLachan AD, Klug A (1985) Repetitive zink-binding domains in the protein transcription factor III A from Xenopus oocytes. EMBO J 4: 1609–1614

    PubMed  CAS  Google Scholar 

  • Mlodzik M, Fjose A, Gehring WJ (1985) Isolation of caudal, a Drosophila homeo box containing gene with maternal expression, whose transcripts form a concentration gradient at the pre-blastoderm stage. EMBO J 4: 2961–2969

    PubMed  CAS  Google Scholar 

  • Nusslein-Volhard C, Wieschaus E (1980) Mutations affecting segment number and polarity in Drosophila. Nature 287: 795–801

    Article  PubMed  CAS  Google Scholar 

  • Odenwald WF, Taylor CF, Palmer-Hill FJ, Friedrich V, Tani M, Lazzarini RA (1987) Expression of a homeo domain protein in non contact-inhibited cultural cells and post mitotic neurons. Genes Dev 1: 482–496

    Article  PubMed  CAS  Google Scholar 

  • Palmiter RD, Brinster RL (1986) Germ-line transformation of mice. Ann Rev Genet 20: 465–499

    Article  PubMed  CAS  Google Scholar 

  • Palmiter RD, Behringer RR, Quaife CJ, Maxwell F, Maxwell IH, Brinster RL (1987) Cell lineage ablation in transgenic mice by cell-specific expression of a toxin gene. Cell 50: 435–443

    Article  PubMed  CAS  Google Scholar 

  • Poole SJ, Kauvar LM, Drees B, Kornberg T (1985) The engrailed locus of Drosophila: structural analysis of an embryonic transcript. Cell 40: 37–43

    Article  PubMed  CAS  Google Scholar 

  • Robertson E, Bradley A, Kuehn MR, Evans MJ (1986) Germ-line transmission of genes introduced into cultured pluripotential cells by retroviral vector. Nature 323: 445–448

    Article  PubMed  CAS  Google Scholar 

  • Roux W (1888) Beiträge zur Entwicklungsmechanik des Embryo. V. Ueber die künstliche Hervorbringung “halber” Embryonen durch Zerstörung einer der beiden ersten Furchungszellen, sowie über die Nachentwicklung (Postgeneration) der fehlenden Körperhälfte. Ges Abh 2: 419–521

    Google Scholar 

  • Rubin MR, King W, Toth LE, Sawczuk IS, Levine MS, D’Eustachio P, Nguyen-Huu MC (1987) The murine hox-1.7 homeobox gene: cloning, chromosomal location, and expression. Mol Cell Biol 7: 3836–3841

    PubMed  CAS  Google Scholar 

  • Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Ehrlich HA (1985) Enzymatic amplification of ß-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 230: 1350–1354

    Article  PubMed  CAS  Google Scholar 

  • Schaffner W (1989) How do different transcription factors binding the same DNA sequence sort out their jobs? TIG 5: 37–39

    Article  PubMed  CAS  Google Scholar 

  • Schulze F, Chowdhury K, Zimmer A, Drescher U, Gruss P (1987) The murine homeobox gene product Hox-1.1 protein is growth-controlled and associated with chromatin. Differentiation 36: 130–137

    Article  PubMed  CAS  Google Scholar 

  • Schulze F, Kessel M, Gruss P (1988) The murine homeobox protein Hox 1.1 is differentially expressed in embryonal mesoderm and ectoderm. In: de Laat SW, Bluemink JG, Mummery CL (eds) Cell to cell signals in mammalian development. NATO ASI Series, Springer, Heidelberg (in press)

    Google Scholar 

  • Scott MP, Weiner AJ (1984) Structural relationships among genes that control development: sequence homology between the Antennapedia, Ultrabithorax and fushi tarazu loci of Drosophila. Proc Natl Acad Sci USA 81: 4115–4119

    Article  PubMed  CAS  Google Scholar 

  • Sharpe PT, Miller JR, Evans EP, Burtenshaw MD, Gaunt SJ (1988) Isolation and expression of a new mouse homeobox gene. Development 102: 397–407

    PubMed  CAS  Google Scholar 

  • Smithies O, Gregg RG, Boggs SS, Koralewski MA, Kucherlapati RS (1985) Insertion of DNA sequences into the human chromosome ß-globin locus by homologous recombination. Nature 317: 230–234

    Article  PubMed  CAS  Google Scholar 

  • Stacey A, Bateman J, Choi T, Mascara T, Cole W, Jaenisch R (1988) Perinatal lethal osteogenesis imperfecta in transgenic mice bearing an engineered mutant proα1(I) collagen gene. Nature 332: 131–136

    Article  PubMed  CAS  Google Scholar 

  • Stern CD, Keynes RJ (1988) Spatial pattern of homeobox gene expression in the developing mammalian CNS. TINS 11: 190–192

    PubMed  CAS  Google Scholar 

  • Theiler K (1972) The house mouse. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Thomas KR, Capecchi MR (1986) Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 51: 503–512

    Article  Google Scholar 

  • Toth LE, Slawin KL, Pintar JE, Nguyen-Huu MC (1987) Region-specific expression of mouse homeobox genes in the embryonic mesoderm and the central nervous system. Proc Natl Acad Sci USA 84: 6790–6794

    Article  PubMed  CAS  Google Scholar 

  • Utset MF, Awgulewitsch A, Ruddle FH, McGinnis W (1987) Region-pecific expression of two homeobox genes. Science 235:1379–1382 Wasylyk B (1988) Transcription elements and factors of RNA polymerase B promoters of higher eukaryotes. CRC Crit Rev Biochem 23:77–120 Zimmer A, Gruss P (1989) Chimeric mice, produced with embryonal stem (ES) cells carrying a homeobox hox 1.1 allele mutated by homologous recombination. Nature (in press)

    Google Scholar 

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Authors and Affiliations

  1. Abteilung Molekulare Zellbiologie, Max-Planck Institut für biophysikalische Chemie, am Faßberg, 3400, Göttingen, Federal Republic of Germany

    Andreas Zimmer & Peter Gruss

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  1. Andreas Zimmer
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  2. Peter Gruss
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  1. Heinrich-Pette-Institut für Virologie und Immunologie, Universität Hamburg, Martinistraße 52, 2000, Hamburg 20, Germany

    Heinz Lother , Rudolf Dernick  & Wolfram Ostertag ,  & 

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Zimmer, A., Gruss, P. (1989). New Strategies in Developmental Biology: In vivo Mutagenesis as a Tool to Dissect Mammalian Development. In: Lother, H., Dernick, R., Ostertag, W. (eds) Vectors as Tools for the Study of Normal and Abnormal Growth and Differentiation. NATO ASI Series, vol 34. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74197-5_3

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  • DOI: https://doi.org/10.1007/978-3-642-74197-5_3

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