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Maintenance of somite borders in mice requires the Delta homologue Dll1

Abstract

During vertebrate embryonic development, the paraxial mesoderm is subdivided into metameric subunits called somites. The arrangement and cranio-caudal polarity of the somites governs the metamerism of all somite-derived tissues and spinal ganglia. Little is known about the molecular mechanisms underlying somite formation, segment polarity, maintenance of segment borders, and the interdependency of these processes. The mouse Delta homologue Dll1, a member of the DSL gene family, is expressed in the presomitic mesoderm and posterior halves of somites1. Here we report that, in Dll1-deficient mouse embryos, a primary metameric pattern is established in mesoderm, and cytodifferentiation is apparently normal, but the segments have no cranio-caudal polarity, and no epithelial somites form. Caudal sclerotome halves do not condense, and the pattern of spinal ganglia and nerves is perturbed, indicating loss of segment polarity. Myoblasts span segment borders, demonstrating that these borders are not maintained. These results show that Dll1 is involved in compartmentalization of somites, that dermomyotome and sclerotome differentiation are independent of formation of epithelia and subdivision of somites in cranial and caudal halves, and that compartmentalization is essential for the maintenance of segment borders in paraxial mesoderm-derived structures.

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References

  1. Bettenhausen, B., Hrabe de Angelis, M., Simon, D., Guenet, J. L. & Gossler, A. Transient and restricted expression during mouse embryogenesis of Dll1, a murine gene closely related to Drosophila Delta Development 21, 2407–2418 (1995).

    Google Scholar 

  2. Campos-Ortega, J. A. Genetic mechanisms of early neurogenesis in Drosophila melanogaster Mol. Neurobiol. 10, 75–89 (1995).

    Article  CAS  Google Scholar 

  3. Chitnis, A., Henrique, D., Lewis, J., Ish, Horowicz, D. & Kintner, C. Primary neurogenesis in Xenopus embryos regulated by a homologue of the Drosophila neurogenic gene Delta. Nature 375, 761–766 (1995).

    Article  ADS  CAS  Google Scholar 

  4. Conlon, R. A., Reaume, A. G. & Rossant, J. Notch1 is required for the coordinate segmentation of somites. Development 121, 1533–1545 (1995).

    CAS  Google Scholar 

  5. Keynes, R. J. & Stern, C. D. Mechanisms of vertebrate segmentation. Development 103, 413–429 (1988).

    CAS  Google Scholar 

  6. Christ, B., Jacob, M., Jacob, H. J., Brand, B. & Wachtler, F. in Somites in Developing Embryos (eds Bellairs, R., Ede, D. A. & Lash, J. W.) 261–275 (Plenum, New York, 1986).

    Book  Google Scholar 

  7. Stern, C. D. & Keynes, R. J. Interactions between somite cells: the formation and maintenance of segment boundaries in the chick embryo. Development 99, 261–272 (1987).

    CAS  Google Scholar 

  8. Keynes, R. J. & Stern, C. D. Segmentation in the vertebrate nervous system. Nature 310, 786–789 (1984).

    Article  ADS  CAS  Google Scholar 

  9. Stern, C. D., Sisodiya, S. M. & Keynes, R. J. Interactions between neurites and somite cells: inhibition and stimulation of nerve growth in the chick embryo. J. Embryol. Exp. Morphol. 91, 209–226 (1986).

    CAS  PubMed  Google Scholar 

  10. Teillet, M. A., Kalcheim, C. & Le Douarin, N. M. Formation of the dorsal root ganglia in the avian embryo: segmental origin and migratory behavior of neural crest progenitor cells. Dev. Biol. 120, 329–347 (1987).

    Article  CAS  Google Scholar 

  11. Davies, J. A., Cook, G. M., Stern, C. D. & Keynes, R. J. Isolation from chick somites of a glycoprotein fraction that causes collapse of dorsal root ganglion growth cones. Neuron 4, 11–20 (1990).

    Article  CAS  Google Scholar 

  12. Goldstein, R. S., Teillet, M. A. & Kalcheim, C. The microenvironment created by grafting rostral half-somites is mitogenic for neural crest cells. Proc. Natl. Acad. Sci. USA 87, 4476–4480 (1990).

    Article  ADS  CAS  Google Scholar 

  13. Burgess, R., Cserjesi, P., Ligon, K. L. & Olson, E. N. Paraxis: a basic helix-loop-helix protein expressed in paraxial mesoderm and developing somites. Dev. Biol. 168, 296–306 (1995).

    Article  CAS  Google Scholar 

  14. Montarras, D. et al. Developmental patterns in the expression of Myf5, MyoD, myogenin, and MRF4 during myogenesis. New Biol. 3, 592–600 (1991).

    CAS  Google Scholar 

  15. Neubüsler, A., Koseki, H. & Balling, R. Characterization and developmental expression of Pax9, a paired-box-containing gene related to Pax1. Dev. Biol. 170, 701–716 (1995).

    Article  Google Scholar 

  16. Koseki, H. et al. A role for Pax-1 as a mediator of notochordal signals during the dorsoventral specification of vertebrae. Development 119, 649–660 (1993).

    CAS  PubMed  Google Scholar 

  17. Candia, A. F. et al. Mox-1 and Mox-2 define a novel homeobox gene subfamily and are differentially expressed during early mesodermal patterning in mouse embryos. Development 116, 1123–1136 (1992).

    CAS  Google Scholar 

  18. Echelard, Y. et al. Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell 75, 1417–1430 (1993).

    Article  CAS  Google Scholar 

  19. Hartenstein, A. Y., Rugendorff, A., Tepass, U. & Hartenstein, V. The function of the neurogenic genes during epithelial development in the Drosophila embryo. Development 116, 1203–1220 (1992).

    CAS  PubMed  Google Scholar 

  20. Burgess, R., Rawls, A., Brown, D., Bradley, A. & Olson, E. Requirement of the paraxis gene for somite formation and muscoskeletal patterning. Nature 384, 570–573 (1966).

    Article  ADS  Google Scholar 

  21. Meinhardt, H. in Somites in Developing Embryos (eds Bellairs, R., Ede, D. A. & Lash, J. W.) 179–189 (Plenum, New York, 1986).

    Book  Google Scholar 

  22. Sambrook, J., Fritsch, E. F. & Maniatis, T. Molecular Cloning: A Laboratory Manual (Spring Harbor Laboratory Press, NY, 1989).

    Google Scholar 

  23. Nagy, A., Rossant, J., Nagy, R., Abramow Newerly, W. & Roder, J. C. Derivation of completely cell culture-derived mice from early-passage embryonic stem cells. Proc. Natl Acad. Sci. USA 90, 8424–8428 (1993).

    Article  ADS  CAS  Google Scholar 

  24. Wilkinson, D. G. in In situ hybridization: A practical approach (ed. Wilkinson, D. G.) 75–84 (Oxford Univ. Press, 1992).

    Google Scholar 

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de Angelis, M., Mclntyre, J. & Gossler, A. Maintenance of somite borders in mice requires the Delta homologue Dll1. Nature 386, 717–721 (1997). https://doi.org/10.1038/386717a0

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