Skip to main content
SpringerLink
Log in

A physical force may expose Hox genes to express in a morphogenetic density gradient

  • Published:
Bulletin of Mathematical Biology Aims and scope Submit manuscript

Abstract

In both invertebrates and vertebrates, a set of homeobox genes is involved in the primary pattern formation along the anterior—posterior axis of the developing organism. In particular, the genes of the Hox/HOM complex are located in a physical order in the 3′ to 5′ direction of the gene clusters. Furthermore, the vertebrate genes of the Hoxa and Hoxd clusters are expressed following the empirical rules of temporal and spatial collinearities: the genes are expressed one after the other according to their positional order and their domains of expression start anteriorly and move gradually towards more posterior locations along the developmental axis. The mechanism that controls this remarkable expression behaviour remains elusive. A proposed morphogen gradient model could justify the serial gene expression in space and time during vertebrate limb development. It is therefore likely that a morphogen concentration ordering might cause the sequential gene expression. I put forward this hypothesis and explore some possibilities that concentration-dependent physical forces might push the Hoxa,d clusters to an environment where the transcriptional activity of the genes is possible. The suggested mechanisms offer satisfactory concentration resolution for differential gene expression. Some experiments are proposed to test the presence of such forces. The verification of this hypothesis would provide a solution to the interpretation problem of the positional information theory in development. Furthermore, it would broaden our knowledge of how gene transcription can be triggered.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Alberts, B., D. Bray, J. Lewis, M. Raff, K. Roberts and J. D. Watson (1994). Molecular Biology of the Cell, 3rd edn, New York: Garland Publishing Inc.

    Google Scholar 

  • Almirantis, Y. and S. Papageorgiou (1999). Modes of morphogen cooperation for limb formation in Vertebrates and Insects. J. Theor. Biol. 199, 235–242.

    Article  Google Scholar 

  • Bailey, C. P., J. M. Dagle and D. L. Weeks (1998). Cationic oligonucleotides can mediate specific inhibition of gene expression in Xenopus oocytes. Nuc. Acids Res. 26, 4860–4867.

    Article  Google Scholar 

  • Belmont, A. S. and K. Bruce (1994). Visualization of G1 chromosomes: a folded, twisted, supercoiled chromonema model of interphase chromatid structure. J. Cell Biol. 127, 287–302.

    Article  Google Scholar 

  • Cremer, T. et al. (1993). Role of chromosome territories in the functional compartmentalization of the cell nucleus. Cold Spring Harb. Symp. Quant. Biol. 58, 777–792.

    Google Scholar 

  • Dagle, J. M. and D. L. Weeks (1996). Positively charged oligonucleotides overcome potassium-mediated inhibition of triple DNA formation. Nuc. Acids Res. 24, 2143–2149.

    Article  Google Scholar 

  • Doering, C., B. Ermentrout and G. Oster (1995). Rotary DNA motors. Biophys. J. 69, 2256–2267.

    Google Scholar 

  • Dollé, P., J.-C. Izpisua-Belmonte, H. Falkenstein, A. Renucci and D. Duboule (1989). Coordinate expression of the murine Hox-5 complex homeobox-containing genes during limb pattern formation. Nature 342, 767–772.

    Article  Google Scholar 

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

    Article  Google Scholar 

  • Driever, W. and C. Nusslein-Volhard (1988b). The bicoid protein determines position in the Drosophila embryo in a concentration-dependent manner. Cell 54, 95–104.

    Article  Google Scholar 

  • Duboule, D. (1992). The vertebrate limb: a model system to study the Hox/HOM gene network during development and evolution. Bioessays 14, 375–384.

    Article  Google Scholar 

  • Duboule, D. (1998). Vertebrate hox gene regulation: clustering and/or colinearity? Curr. Opin. Genet. Dev. 8, 514–518.

    Article  Google Scholar 

  • Gehring, W. (1998). Master Control Genes in Development and Evolution: The Homeobox Story, New Haven: Yale University Press.

    Google Scholar 

  • Gordon, R. (1987). A retaliatory role for algal projectiles, with implications for the mechanochemistry of diatom gliding motility. J. Theor. Biol. 126, 419–436.

    Google Scholar 

  • Gordon, R. (1999). The Hierarchical Genome and Differentiation Waves, London: World Scientific.

    Google Scholar 

  • Green, J. B. A., H. V. New and J. C. Smith (1992). Responses of embryonic Xenopus cells to Activin and FGF are separated by multiple dose thresholds and correspond to distinct axes of the mesoderm. Cell 71, 731–739.

    Article  Google Scholar 

  • Gurdon, J. B., A. Mitchell and K. Ryan (1996). An experimental system for analyzing response to a morphogen gradient. Proc. Natl. Acad. Sci. USA 93, 9334–9338.

    Article  Google Scholar 

  • Harding, S. E. (1997). The intrinsic viscosity of biological macromolecules. Progress in measurement, interpretation and application to structure in dilute solution. Prog. Biophys. Mol. Biol. 68, 207–262.

    Article  Google Scholar 

  • Iwata, T., S. Minucci, M. McGowan and D. Carper (1997). Identification of a novel cis-element required for the constitutive activity and osmotic response of the rat aldose reductase promoter. J. Biol. Chem. 272, 32500–32506.

    Google Scholar 

  • Jackson, J. D. (1975). Classical Electrodynamics, 2nd edn, New York: John Wiley.

    MATH  Google Scholar 

  • Kerszberg, M. and L. Wolpert (1998). Mechanisms for signalling by morphogen transport: a theoretical study. J. Theor. Biol. 191, 103–114.

    Article  Google Scholar 

  • Kessel, M. and P. Gruss (1991). Homeotic transformations of murine vertebrae and concomitant alteration of Hox codes induced by retinoic acid. Cell 67, 89–104.

    Article  Google Scholar 

  • Kondo, T., J. Zakany and D. Duboule (1998). Control of colinearity in AbdB genes of the mouse HoxD complex. Mol. Cell 1, 289–300.

    Article  Google Scholar 

  • Krumlauf, R. (1994). Hox genes in vertebrate development. Cell 78, 191–201.

    Article  Google Scholar 

  • Kumar-Singh, R. and J. S. Chamberlain (1996). Encapsidated adenovirus minichromosomes allow delivery and expression of a 14 kb dystrophin cDNA to muscle cells. Hum. Mol. Genet. 5, 913–921.

    Article  Google Scholar 

  • Kurz, A., S. Lampel, J. E. Nickolenko, J. Bradl, A. Brenner, R. M. Zirbel, T. Cremer and P. Lichter (1996). Active and inactive genes localize preferentially in the periphery of chromosome territories. J. Cell Biol. 135, 1195–2005.

    Article  Google Scholar 

  • Lawrence, J. B., R. H. Singer and J. A. McNeil (1990). Interphase and metaphase resolution of different distances within the human dystrophin gene. Science 249, 928–932.

    Google Scholar 

  • Lawrence, P. A. and G. Struhl (1996). Morphogens, compartments and patterns: lessons from Drosophila? Cell 85, 951–961.

    Article  Google Scholar 

  • Lecuit, T. and S. M. Cohen (1997). Proximal-distal axis formation in the Drosophila leg. Nature 388, 139–144.

    Article  Google Scholar 

  • Lewin, B. (1997). Genes VI, Oxford: Oxford University Press.

    Google Scholar 

  • Lewis, J., J. M. W. Slack and L. Wolpert (1977). Thresholds in development. J. Theor. Biol. 65, 579–590.

    Article  Google Scholar 

  • MacWilliams, H. K. and S. Papageorgiou (1978). A model gradient interpretation based on morphogen binding. J. Theor. Biol. 72, 385–411.

    Article  Google Scholar 

  • Margeat, E., C. LeGrimellec and C. A. Royer (1998). Visualization of trp repressor and its complexes with DNA by atomic force microscopy. Biophys. J. 75, 2712–2720.

    Google Scholar 

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

    Article  Google Scholar 

  • Montijn, M. B., A. B. Houtsmuller, R. ten Hoopen, J. L. Oud and N. Nanninga (1999). The 5S rRNA gene clusters have a defined orientation toward the nucleolus in Petunia hybrida and Crepis capillaris. Chromosome Res. 7, 387–399.

    Article  Google Scholar 

  • Munkel, C., R. Eils, S. Dietzel, D. Zink, C. Mehring, G. Wedemann, T. Cremer and J. Langowski (1999). Compartmentalization of interphase chromosomes observed in simulation and experiment. J. Mol. Biol. 285, 1053–1065.

    Article  Google Scholar 

  • Murray, J. D. (1989). Mathematical Biology, Berlin: Springer-Verlag.

    MATH  Google Scholar 

  • Nakielny, S. and G. Dreyfuss (1999). Transport of proteins and RNAs in and out of the nucleus. Cell 99, 677–690.

    Article  Google Scholar 

  • Nelson, C. E., B. A. Morgan, A. C. Burke, E. Laufer, E. Dimambro, L. C. Murtaugh, E. Gonzalez, L. Tessarollo, L. F. Parada and C. Tabin (1996). Analysis of Hox gene expression in the chick limb bud. Development 122, 1449–1466.

    Google Scholar 

  • Niswander, L., S. Jeffrey, G. R. Martin and C. Tickle (1994). A positive feedback loop coordinates growth and patterning in the vertebrate limb. Nature 371, 609–612.

    Article  Google Scholar 

  • Orlando, V., E. P. Jane, V. Chinwalla, P. J. Harte and R. Paro (1998). Binding of trithorax and Polycomb proteins to the bithorax complex: dynamic changes during early Drosophila embryogenesis. EMBO J. 17, 5141–5150.

    Article  Google Scholar 

  • Orlando, V. and R. Paro (1993). Mapping Polycomb-repressed domains in the bithorax complex using in vivo formaldehyde cross-linked chromatin. Cell 75, 1187–1198.

    Article  Google Scholar 

  • Papageorgiou, S. (1998). Cooperating morphogens control hoxd gene expression in the developing vertebrate limb. J. Theor. Biol. 192, 43–53.

    Google Scholar 

  • Papageorgiou, S. and Y. Almirantis (1996). Gradient model describes the spatial-temporal expression pattern of Hoxa genes in the developing vertebrate limb. Dev. Dyn. 207, 461–469.

    Article  Google Scholar 

  • Papageorgiou, S. and Y. Almirantis (1998). Universality of combined morphogen action for the limb axes formation in Vertebrates and Insects. Dev. Biol. 198, 185.

    Google Scholar 

  • Papin, C. and J. C. Smith (2000). Gradual refinement of activin-induced thresholds requires protein synthesis. Dev. Biol. 217, 166–172.

    Article  Google Scholar 

  • Passner, J. M., H. D. Ryoo, L. Shen, R. S. Mann and A. K. Aggarwal (1999). Structure of a DNA-bound-Ultrabithorax-Extradenticle homeodomain complex. Nature 397, 714–719.

    Article  Google Scholar 

  • Rashevsky, N. (1960). Mathematical Biophysics, Vol. I, New York: Dover.

    Google Scholar 

  • Schlossherr, J., H. Eggert, R. Paro, S. Cremer and R. S. Jack (1994). Gene inactivation in Drosophila mediated by the Polycomb gene product or by position-effect variegation does not involve major changes in the accessibility of the chromatin fibre. Mol. Gen. Genet. 243, 453–462.

    Google Scholar 

  • Singer, M. and P. Berg (1991). Genes and Genomes, CA: University Science Books.

    Google Scholar 

  • Strauss-Soukup, J. K. and L. J. Maher 3rd (1998). Electrostatic effects in DNA bending by GCN4 mutants. Biochemistry 37, 1060–1067.

    Article  Google Scholar 

  • Struhl, G. (1984). Splitting the bithorax complex of Drosophila. Nature 308, 454–457.

    Article  Google Scholar 

  • Tumbar, T., G. Sudlow and A. S. Belmont (1999). Large-scale chromatin unfolding and remodeling induced by VP16 acid activation domain. J. Cell Biol. 145, 1341–1354.

    Article  Google Scholar 

  • van der Hoeven, F., J. Zakany and D. Duboule (1996). Gene transpositions in the Hoxd complex reveal a hierarchy of regulatory controls. Cell 85, 1025–1035.

    Article  Google Scholar 

  • Vargesson, N., K. Kostakopoulou, G. Drossopoulou, S. Papageorgiou and C. Tickle (2000). Characterisation of Hoxa gene expression in the chick limb bud in response to FGF. Dev. Dyn. (to be published).

  • Veguchi, C. and T. Mizuno (1993). The Escherichia coli nucleotid protein H-NS functions directly as a transcriptional repressor. EMBO J. 12, 1039–1046.

    Google Scholar 

  • Wang, W., J. Lin and D. C. Schwartz (1998). Scanning force microscopy of DNA molecules elongated by convective fluid flow in an evaporating droplet. Biophys. J. 75, 513–520.

    Google Scholar 

  • Wolpert, L. (1969). Positional information and the spatial pattern of cellular differentiation. J. Theor. Biol. 25, 1–47.

    Google Scholar 

  • Wolpert, L. (1996). One hundred years of positional information. Trends Genet. 12, 359–364.

    Article  Google Scholar 

  • Wuhrmann, P., H. Ineichen, U. Riesen-Willi and M. Lezzi (1979). Change in nuclear potassium electrochemical activity and puffing of potassium-sensitive salivery chromosome regions during Chironomus development. Proc. Natl. Acad. Sci. USA 76, 806–808.

    Article  Google Scholar 

  • Yokouchi, Y., H. Sasaki and A. Kuroiwa (1991). Homeobox gene expression correlated with the bifurcation process of limb cartilage development. Nature 353, 443–445.

    Article  Google Scholar 

  • Zhang, W., H. Ni, M. W. Capp, C. F. Anderson, T. M. Lohman and M. T. Record Jr (1999). The importance of Coulombic end effects: experimental characterization of the effects of oligonucleotide flanking charges on the strength and salt dependence of oligocation (L8+) binding to single-stranded DNA oligomers. Biophys. J. 76, 1008–1017.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Biology, N.R.C. ‘Demokritos’, 153 10, Aghia Paraskevi, Athens, Greece

    Spyros Papageorgiou

Authors
  1. Spyros Papageorgiou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Spyros Papageorgiou.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Papageorgiou, S. A physical force may expose Hox genes to express in a morphogenetic density gradient. Bull. Math. Biol. 63, 185–200 (2001). https://doi.org/10.1006/bulm.2000.0211

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1006/bulm.2000.0211

Keywords

Search

Navigation