Skip to main content
SpringerLink
Log in

Genetic Mechanisms Responsible for Pattern Formation in the Vertebrate Hindbrain: Regulation of Hoxb-1

  • Chapter
Neural Cell Specification

Part of the book series: Altschul Symposia Series ((ALSS,volume 3))

Abstract

During development of the vertebrate nervous system a process of segmentation, that will give rise to the generation of morphologically repeated units called rhombomeres (r), occurs in the hindbrain (reviewed in Lumsden, 1990; Wilkinson and Krumlauf, 1990). The formation of rhombomeres is correlated with the process of neurogenesis involving the reticular formation and the branchial motor system. Each branchial motor nucleus occupies a distinct position in the hindbrain and is derived from neurons in two adjacent rhombomeres. These neurons lie in register with the appropriate branchial arch, in a two-segment repetition pattern (Lumsden and Keynes, 1989). Boundaries between even and odd numbered rhombomeres are formed progressively in an order that does not follow a strict anterior to posterior progression (Vaage, 1969; Lumsden, 1990). To understand more about the establishment and formation of rhombomere boundaries, cell lineage studies have been performed in the chick. Single cell labelling experiments have shown that cell mixing only occurs between neighbouring segments before the boundaries between future odd and even numbered rhombomeres are formed (Wilkinson et al., 1989a; Guthrie and Lumsden, 1991; Guthrie et al., 1993). After boundary formation, rhombomeres become lineage-restricted cellular compartments, where cells are committed to a specific segment, hence each segment can maintain a distinct regional identity (Fraser et al., 1990; Birgbauer and Fraser, 1994).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Akam M (1987): The molecular basis for metameric pattern in the Drosophila embryo. Development 101: 1–22.

    PubMed  CAS  Google Scholar 

  • Awgulewitsch A and Jacobs D (1992): Deformed autoregulatory element from Drosophila functions in a conserved manner in transgenic mice. Nature 358: 341–345.

    Article  PubMed  CAS  Google Scholar 

  • Birgbauer E and Fraser SE (1984): Violation of cell lineage restriction compartments in the chick hindbrain. Development 120: 1347–1356.

    Google Scholar 

  • Boncinelli E, Somma R, Acampora D, Pannese M, D’Esposito M, Faiella A and Simeone A (1988): Organization of human homeobox genes. Hum Reprod 3: 880–886.

    PubMed  CAS  Google Scholar 

  • Boncinelli E, Simeone A, Acampora D and Mavilio F (1991): HOX gene activation by retinoic acid. TIG 7: 329–334.

    PubMed  CAS  Google Scholar 

  • Carpenter E, Goddard J, Chisaka O, Manley N and Capecchi M (1993): Loss of Hox-al (Hox-1.6) function results in reorganisation of the murine hindbrain. Development 118: 1063–1075.

    PubMed  CAS  Google Scholar 

  • Chisaka O, Musci T and Capecchi M (1992): Developmental defects of the ear, cranial nerves and hindbrain resulting from targeted disruption of the mouse homeobox gene Hox-1.6. Nature 355: 516–520.

    Article  PubMed  CAS  Google Scholar 

  • Conlon R and Rossant J (1992): Exogenous retinoic acid rapidly induces anterior ectopic expression of murine Hox-2 genes in vivo. Development 116: 357–368.

    PubMed  CAS  Google Scholar 

  • Dekker E-J, Pannese M, Houtzager E, Boncinelli E and Durston A (1993): Colinearity in the Xenopus laevis Hox-2 complex. Mech Development 40: 3–12.

    Article  CAS  Google Scholar 

  • Dollé P, Lufkin T, Krumlauf R, Mark M, Duboule D and Chambon P (1993): Local alterations of Krox-20 and Hox gene expression in the hindbrain of Hox-al (Hox-1.6) homozygote null mutant embryos. Proc Natl Acad Sci USA 90: 7666–7670.

    Article  PubMed  Google Scholar 

  • Duboule D and Dollé P (1989): The structural and functinal organization of the murine HOX gene family resembles that of Drosophila homeotic genes. EMBO J 8: 1497–1505.

    PubMed  CAS  Google Scholar 

  • Fraser S, Keynes R and Lumsden A (1990): Segmentation in the chick embryo hindbrain is defined by cell lineage restrictions. Nature 344: 431–435.

    Article  PubMed  CAS  Google Scholar 

  • Frohman M, Boyle M and Martin G (1990): Isolation of the mouse Hox-2.9 gene; analysis of embryonic expression suggests that positional information along the anterior-posterior axis is specified by mesoderm. Development 110: 589–607.

    PubMed  CAS  Google Scholar 

  • Graham A, Papalopulu N and Krumlauf R (1989): The murine and Drosophila homeobox clusters have common features of organisation and expression. Cell 57: 367–378.

    Article  PubMed  CAS  Google Scholar 

  • Guthrie S and Lumsden A (1991): Formation and regeneration of rhombomere boundaries in the developing chick hindbrain. Development 112: 221–229.

    PubMed  CAS  Google Scholar 

  • Guthrie S, Muchamore I, Marshall H, Kuroiwa A, Krumlauf R and Lumsden A (1992): Neuroectodermal autonomy of Hox-2.9 expression revealed by rhombomere transpositions. Nature 356: 157–159.

    Article  PubMed  CAS  Google Scholar 

  • Guthrie S, Prince V and Lumsden A (1993): Selective dispersal of avian rhombomere cells in orthotopic and heterotopic grafts. Development 118: 527–538.

    PubMed  CAS  Google Scholar 

  • Hunt P, Gulisano M, Cook M, Sham MH, Faiella A, Wilkinson D, Boncinelli E and Krumlauf R (1991): A distinct Hox code for the branchial region of the head. Nature 353: 861–864.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Ip YT, Levine M and Small SJ (1992): The bicoid and dorsal morphogens use a similar strategy to make stripes in the Drosophila embryo. J Cell Sci 16(Suppl): 33–38.

    CAS  Google Scholar 

  • Izpisua-Belmonte J, Falkenstein H, Dolle P, Renucci A and Duboule D (1991): Murine genes related to the Drosophila AbdB homeotic gene are sequentially expressed during development of the posterior part of the body. Embo J 10: 2279–2289.

    PubMed  CAS  Google Scholar 

  • Jackie H, Hoch M, Pankratz MJ, Gerwin N, Sauer F and Bronner G (1992): Transcriptional control by Drosophila gap genes. J Cell Sci 16(Suppl): 39–51.

    Google Scholar 

  • Kessel M (1993): Reversal of axonal pathways from rhombomere 3 correlates with extra Hox expression domains. Neuron 10: 379–393.

    Article  PubMed  CAS  Google Scholar 

  • Kliewer SA, Umesono K, Mangelsdorf DJ and Evans RM (1992): Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling. Nature 355: 446–449.

    Article  PubMed  CAS  Google Scholar 

  • Krumlauf R (1992): Evolution of the vertebrate Hox homeobox genes. Bioessays 14: 245–252.

    Article  PubMed  CAS  Google Scholar 

  • Kuratani SC and Eichele G (1993): Rhombomere transposition repatterns the segmental organization of cranial nerves and reveals cell-autonomous expression of a homeodomain protein. Development 117: 105–117.

    PubMed  CAS  Google Scholar 

  • Langston AW and Gudas LJ (1992): Identification of a retinoic acid responsive enhancer 3’ of the murine homeobox gene Hox-1.6. Mech Dev 38: 217–228.

    Article  PubMed  CAS  Google Scholar 

  • Leid M Kastner P and Chambon P (1992): Multiplicity generates diversity in the retinoic acid signalling pathways. Trends Biochem Sci 17: 427–433.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Lohnes D, Kastner P, Dierich A, Mark M, LeMeur M and Chambon P (1993): Function of retinoic acid receptor g in the mouse. Cell 73: 643–658.

    Article  PubMed  CAS  Google Scholar 

  • Lufkin T, Dierich A, LeMeur M, Mark M and Chambon P (1991): Disruption of the Hox1.6 homeobox gene results in defects in a region corresponding to its rostral domain of expression. Cell 66: 1105–1119.

    Article  PubMed  CAS  Google Scholar 

  • Lumsden A (1990): The cellular basis of segmentation in the developing hindbrain. Trends Neurosci 13: 329–335.

    Article  PubMed  CAS  Google Scholar 

  • Lumsden A and Keynes R (1989): Segmental patterns of neuronal development in the chick hindbrain. Nature 337: 424–428.

    Article  PubMed  CAS  Google Scholar 

  • Malicki J, Cianetti L, Peschle C and McGinnis W (1992): A human HOX 4B regulatory element provides head-specific expression in Drosophila embryos. Nature 358: 345–347.

    Article  PubMed  CAS  Google Scholar 

  • Mark M, Lufkin T, Vonesch J-L, Ruberte E, Olivo J-C, Dollé P, Gorry P, Lumsden A and Chambon P (1993): Two rhombomeres are altered in Hox-al null mutant mice. Development 119: 319–338.

    PubMed  CAS  Google Scholar 

  • Marshall H, Nonchev S, Sham M-H, Muchamore I, Lumsden A and Krumlauf R (1992): Retinoic acid alters the hindbrain Hox code and induces the transformation of rhombomeres 2/3 into a rhombomere 4/5 identity. Nature 360: 737–741.

    Article  PubMed  CAS  Google Scholar 

  • Marshall H, Studer M, Pöpperl H, Aparicio S, Kuroiwa A, Brenner S and Krumlauf R (1994): A conserved retinoic acid response element required for early expression of the homeobox gene Hoxb-1. Nature 370: 567–571.

    Article  PubMed  CAS  Google Scholar 

  • McGinnis W and Krumlauf R (1992): Homeobox genes and axial patterning. Cell 68: 283–302.

    Article  PubMed  CAS  Google Scholar 

  • Morriss-Kay G (1993): Retinoic acid and craniofacial development: molecules and morphogenesis. Bioessays 15: 9–15.

    Article  PubMed  CAS  Google Scholar 

  • Morriss-Kay G, Murphy P, Hill R and Davidson D (1991): Effects of retinoic acid on expression of Hox 2.9 and Krox 20 and on morphological segmentation in the hindbrain of mouse embryos. EMBO J 10: 2985–2996.

    PubMed  CAS  Google Scholar 

  • Murphy P and Hill R (1991): Expression of mouse labial-like homeobox-containing genes, Hox 2.9 and Hox 1.6, during segmentation of the hindbrain. Development 111: 61–74.

    PubMed  CAS  Google Scholar 

  • Murphy P, Davidson D and Hill R (1989): Segment-specific expression of a homeoboxcontaining gene in the mouse hindbrain. Nature 341: 156–159.

    Article  PubMed  CAS  Google Scholar 

  • Papalopulu N, Lovell-Badge R and Krumlauf R (1991): The expression of murine Hox-2 genes is dependent on the differentiation pathway and displays collinear sensitivity to retinoic acid in F9 cells and Xenopus embryos. Nucleic Acid Res 19: 5497–5506.

    Article  PubMed  CAS  Google Scholar 

  • Puschel A, Balling R and Gruss P (1990): Postion-specific activity of the Hox 1.1 promoter in transgenic mice. Development 108: 435–442.

    PubMed  CAS  Google Scholar 

  • Schneider-Maunoury S, Topilko P, Seitanidou T, Levi G, Cohen-Tannoudji M, Pournin S, Babinet C and Charnay P (1993): Disruption of Krox-20 results in elimination of rhombomeres 3 and 5 in the developing hindbrain. Cell 75: 1199–1214.

    Article  PubMed  CAS  Google Scholar 

  • Scott MP (1992): Vertebrate Homeobox Gene Nomenclature. Cell 71: 551–553.

    Article  PubMed  CAS  Google Scholar 

  • Scott MP, Tamkun JW and Hartzell GW 3rd (1989): The structure and function of the homeodomain. Biochim. Biophys. Acta 989: 25–48.

    CAS  Google Scholar 

  • Sham M-H, Hunt P, Nonchev S, Papalopulu N, Graham A, Boncinelli E and Krumlauf R (1992): Analysis of the murine Hox-2.7 gene: conserved alternative transcripts with differential distributions in the nervous system and the potential for shared regulatory regions. EMBO J 11: 1825–1836.

    PubMed  CAS  Google Scholar 

  • Sham MH, Vesque C, Nonchev S, Marshall H, Frain M, Das Gupta R, Whiting J, Wilkinson D, Charnay P and Krumlauf R (1993): The zinc finger gene Krox-20 regulates Hox-b2 during hindbrain segmentation. Cell 72: 183–196.

    Article  PubMed  CAS  Google Scholar 

  • Simeone A, Acampora D, Arcioni L, Andrews PW, Boncinelli E and Mavilio F (1990): Sequential activation of HOX2 homeobox genes by retinoic acid in human embryonal carcinoma cells. Nature 346: 763–766.

    Article  PubMed  CAS  Google Scholar 

  • Simeone A, Acampora D, Nigro V, Faiella A, D’Esposito M, Stornaiuolo A, Mavilio F and Boncinelli E (1991): Differential regulation by retinoic acid of the homeobox genes of the four HOX loci in human embryonal carcinoma cells. Mech Develop 33: 215–227.

    Article  CAS  Google Scholar 

  • Studer M, Pöpperl M, Marshall H, Kuroiwa A and Krumlauf R (1994): Role of conserved retinoic response element in rhombomeric restriction of Hoxb-1. Science 265: 1728–1732.

    Article  PubMed  CAS  Google Scholar 

  • Stunnenberg H (1993): Mechanisms of transactivation by retinoic acid receptors. Bioessays 15: 309–315.

    Article  PubMed  CAS  Google Scholar 

  • Sundin O and Eichele G (1990): A horneo domain protein reveals the metameric nature of the developing chick hindbrain. Genes Dev 4: 1267–1276.

    Article  PubMed  CAS  Google Scholar 

  • Sundin O and Eichele G (1992): An early marker of axial pattern in the chick embryo and its respecification by retinoic acid. Development 114: 841–852.

    PubMed  CAS  Google Scholar 

  • Swiatek PJ and Gridley T (1993): Perinatal lethality and defects in hindbrain development in mice homozygous for a targeted mutation of the zinc finger gene Krox 20. Genes Dev 7: 2071–2084.

    Article  PubMed  CAS  Google Scholar 

  • Vaage S (1969): The segmentation of the primitive neural tube in chick embryos (Gallus domesticus). Adv Anat Embryol Cell Biol 41: 1–88.

    Google Scholar 

  • Whiting J, Marshall H, Cook M, Krumlauf R, Rigby P, Stott D and Allemann R (1991): Multiple spatially-specific enhancers are required to reconstruct the pattern of Hox2.6 gene expression. Genes Dev 5: 2048–2059.

    Article  PubMed  CAS  Google Scholar 

  • Wilkinson D and Krumlauf R (1990): Molecular approaches to the segmentation of the hindbrain. Trends Neurosci 13: 335–339.

    Article  PubMed  CAS  Google Scholar 

  • Wilkinson D, Bhatt S, Chavrier P, Bravo R and Charnay P (1989a): Segment-specific expression of a zinc finger gene in the developing nervous system of the mouse. Nature 337: 461–464.

    Article  CAS  Google Scholar 

  • Wilkinson D, Bhatt S, Cook M, Boncinelli E and Krumlauf R (1989b): Segmental expression of Hox 2 homeobox-containing genes in the developing mouse hindbrain. Nature 341: 405–409.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Developmental Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 IAA, UK

    Michèle Studer, Heather Marshall, Heike Pöpperl & Robb Krumlauf

  2. Department of Molecular Biology, School of Science, Nagoya University, Chihusa-Ku, Nagoya, Japan

    Atsushi Kuroiwa

Authors
  1. Michèle Studer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Heather Marshall
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Heike Pöpperl
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Atsushi Kuroiwa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Robb Krumlauf
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Saskatchewan, Saskatoon, Saskatchewan, Canada

    J. Ronald Doucette

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Springer Science+Business Media New York

About this chapter

Cite this chapter

Studer, M., Marshall, H., Pöpperl, H., Kuroiwa, A., Krumlauf, R. (1995). Genetic Mechanisms Responsible for Pattern Formation in the Vertebrate Hindbrain: Regulation of Hoxb-1. In: Juurlink, B.H.J., Krone, P.H., Kulyk, W.M., Verge, V.M.K., Doucette, J.R. (eds) Neural Cell Specification. Altschul Symposia Series, vol 3. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1929-4_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-1929-4_2

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5790-2

  • Online ISBN: 978-1-4615-1929-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation