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FGF receptor signalling is required to maintain neural progenitors during Hensen's node progression

Abstract

Previous analyses of labelled clones of cells within the developing nervous system of the mouse have indicated that descendants are initially dispersed rostrocaudally followed by more local proliferation, which is consistent with the progressing node's contributing descendants from a resident population of progenitor cells as it advances caudally. Here we electroporated an expression vector encoding green fluorescent protein into the chicken embryo near Hensen's node to test and confirm the pattern inferred in the mouse. This provides a model in which a proliferative stem zone is maintained in the node by a localized signal; those cells that are displaced out of the stem zone go on to contribute to the growing axis. To test whether fibroblast growth factor (FGF) signalling could be involved in the maintenance of the stem zone, we co-electroporated a dominant-negative FGF receptor with a lineage marker, and found that it markedly alters the elongation of the spinal cord primordium. The results indicate that FGF receptor signalling promotes the continuous development of the posterior nervous system by maintaining presumptive neural progenitors in the region near Hensen's node. This offers a potential explanation for the mixed findings on FGF in the growth and patterning of the embryonic axis.

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Figure 1: Electroporation of the spinal cord primordium to assay elongation.
Figure 2: A similar pattern of elongation throughout spinal cord formation.
Figure 3: Posterior progression of spinal cord progenitors resident in the node region.
Figure 4: Phenotypes produced by expression of dnFGFr.
Figure 5: Expression of dnFGFr disrupts polyclone elongation.
Figure 6: Elongation of the population expressing dnBMPr.

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References

  1. Lumsden, A. & Krumlauf, R. Patterning the vertebrate neuraxis. Science 274, 1109–1114 (1996).

    Article  CAS  Google Scholar 

  2. Harland, R. & Gerhart, J. Formation and function of Spemann's organizer. Annu. Rev. Cell. Dev. Biol. 13, 611–667 (1997).

    Article  CAS  Google Scholar 

  3. Smith, J. L. & Schoenwolf, G. C. Getting organized: new insights into the organizer of higher vertebrates. Curr. Top. Dev. Biol. 40, 79–110 (1998).

    Article  CAS  Google Scholar 

  4. Woo, K. & Fraser, S. E. Specification of the zebrafish nervous system by nonaxial signals. Science 277, 254–257 (1997).

    Article  CAS  Google Scholar 

  5. Rowan, A. M., Stern, C. D. & Storey, K. G. Axial mesendoderm refines rostrocaudal pattern in the chick nervous system. Development 126, 2921–2934 (1999).

    CAS  PubMed  Google Scholar 

  6. Bouwmeester, T. & Leyns, L. Vertebrate head induction by anterior primitive endoderm. BioEssays 19, 855–863 (1997).

    Article  CAS  Google Scholar 

  7. Beddington, R. S. & Robertson, E. J. Axis development and early asymmetry in mammals. Cell 96, 195–209 (1999).

    Article  CAS  Google Scholar 

  8. Woo, K. & Fraser, S. E. Specification of the hindbrain fate in the zebrafish. Dev. Biol. 197, 283–296 (1998).

    Article  CAS  Google Scholar 

  9. Darnell, D. K., Stark, M. R. & Schoenwolf, G. C. Timing and cell interactions underlying neural induction in the chick embryo. Development 126, 2505–2514 (1999).

    CAS  PubMed  Google Scholar 

  10. Nieuwkoop, P. D. Activation and organization of the central nervous system in amphibians. Part III. Synthesis of a new working hypothesis. J. Exp. Zool. 120, 83–108 (1952).

    Article  Google Scholar 

  11. Doniach, T. Basic FGF as an inducer of anteroposterior neural pattern. Cell 83, 1067–1070 (1995).

    Article  CAS  Google Scholar 

  12. Lamb, T. M. & Harland, R. M. Fibroblast growth factor is a direct neural inducer, which combined with noggin generates anterior–posterior neural pattern. Development 121, 3627–3636 (1995).

    CAS  PubMed  Google Scholar 

  13. Cox, W. G. & Hemmati-Brivanlou, A. Caudalization of neural fate by tissue recombination and bFGF. Development 121, 4349–4358 (1995).

    CAS  PubMed  Google Scholar 

  14. Kengaku, M. & Okamoto, H. bFGF as a possible morphogen for the anteroposterior axis of the central nervous system in Xenopus. Development 121, 3121–3130 (1995).

    CAS  PubMed  Google Scholar 

  15. Kroll, K. L. & Amaya, E. Transgenic Xenopus embryos from sperm nuclear transplantations reveal FGF signaling requirements during gastrulation. Development 122, 3173–3183 (1996).

    CAS  PubMed  Google Scholar 

  16. Keller, R. & Danilchik, M. Regional expression, pattern and timing of convergence and extension during gastrulation of Xenopus laevis. Development 103, 193–209 (1988).

    CAS  PubMed  Google Scholar 

  17. Mathis, L. & Nicolas, J. F. Different clonal dispersion in the rostral and caudal mouse central nervous system. Development 127, 1277–1290 (2000).

    CAS  PubMed  Google Scholar 

  18. Schoenwolf, G. C. & Alvarez, I. S. Roles of neuroepithelial cell rearrangement and division in shaping of the avian neural plate. Development 106, 427–439 (1989).

    CAS  PubMed  Google Scholar 

  19. Alvarez, I. S. & Schoenwolf, G. C. Patterns of neurepithelial cell rearrangement during avian neurulation are determined prior to notochordal inductive interactions. Dev. Biol. 143, 78–92 (1991).

    Article  CAS  Google Scholar 

  20. Hatada, Y. & Stern, C. D. A fate map of the epiblast of the early chick embryo. Development 120, 2879–2889 (1994).

    CAS  PubMed  Google Scholar 

  21. Catala, M., Teillet, M. A., De Robertis, E. M. & Le Douarin, M. L. A spinal cord fate map in the avian embryo: while regressing, Hensen's node lays down the notochord and floor plate thus joining the spinal cord lateral walls. Development 122, 2599–2610 (1996).

    CAS  PubMed  Google Scholar 

  22. Henrique, D. et al. cash4, a novel achaete-scute homolog induced by Hensen's node during generation of the posterior nervous system. Genes Dev. 11, 603–615 (1997).

    Article  CAS  Google Scholar 

  23. Kimmel, C. B., Warga, R. M. & Kane, D. A. Cell cycles and clonal strings during formation of the zebrafish central nervous system. Development 120, 265–276 (1994).

    CAS  PubMed  Google Scholar 

  24. Woo, K. & Fraser, S. E. Order and coherence in the fate map of the zebrafish nervous system. Development 121, 2595–2609 (1995).

    CAS  PubMed  Google Scholar 

  25. Eagleson, G. W. & Harris, W. A. Mapping of the presumptive brain regions in the neural plate of Xenopus laevis. J. Neurobiol. 21, 427–440 (1990).

    Article  CAS  Google Scholar 

  26. Keller, R., Shih, J. & Sater, A. The cellular basis of the convergence and extension of the Xenopus neural plate. Dev. Dyn. 193, 199–217 (1992).

    Article  CAS  Google Scholar 

  27. Itasaki, N., Bel, V. S. & Krumlauf, R. 'Shocking' developments in chick embryology: electroporation and in ovo gene expression. Nature Cell Biol. 1, E203–E207 (1999).

    Article  CAS  Google Scholar 

  28. Schoenwolf, G. C. Observations on closure of the neuropores in the chick embryo. Am. J. Anat. 4, 445–465 (1979).

    Article  Google Scholar 

  29. Watt, F. M. & Hogan, B. L. Out of Eden: stem cells and their niches. Science 287, 1427–1430 (2000).

    Article  CAS  Google Scholar 

  30. Ueno, H., Gunn, M., Dell, K., Tseng, A., Jr, Williams, L. A truncated form of fibroblast growth factor receptor 1 inhibits signal transduction by multiple types of fibroblast growth factor receptor. J. Biol. Chem. 267, 1470–1476 (1992).

    CAS  PubMed  Google Scholar 

  31. Amaya, E., Musci, T. J. & Kirschner, M. W. Expression of a dominant-negative mutant of the FGF receptor disrupts mesoderm formation in Xenopus embryos. Cell 66, 257–270 (1991).

    Article  CAS  Google Scholar 

  32. Zou, H. & Niswander, L. Requirement for BMP signaling in interdigital apoptosis and scale formation. Science 272, 738–741 (1996).

    Article  CAS  Google Scholar 

  33. Selleck, M. A. & Stern, C. D. in Formation and Differentiation of Early Embryonic Mesoderm (ed. R. Bellairs) 23–31 (Plenum, New York, 1992).

    Book  Google Scholar 

  34. Beddington, R. S. Induction of a second neural axis by the mouse node. Development 120, 613–620 (1994).

    CAS  PubMed  Google Scholar 

  35. Nicolas, J. F., Mathis, L. & Bonnerot, C. Evidence in the mouse for self-renewing stem cells in the formation of a segmented longitudinal structure, the myotome. Development 122, 2933–2946 (1996).

    CAS  PubMed  Google Scholar 

  36. Psychoyos, D. & Stern, C. D. Fates and migratory routes of primitive streak cells in the chick embryo. Development 122, 1523–1534 (1996).

    CAS  PubMed  Google Scholar 

  37. Davidson, B. P., Kinder, S. J., Steiner, K., Schoenwolf, G. C. & Tam, P. P. Impact of node ablation on the morphogenesis of the body axis and the lateral asymmetry of the mouse embryo during early organogenesis. Dev. Biol. 211(1), 11–26 (1999).

    Article  Google Scholar 

  38. Brown, J. M. & Storey, K. G. A region of the vertebrate neural plate in which neighbouring cells can adopt neural or epidermal fates. Curr. Biol. 10, 869–872 (2000).

    Article  CAS  Google Scholar 

  39. Yamaguchi, T. P., Conlon, R. A. & Rossant, J. Expression of the fibroblast growth factor receptor FGFR-1/flg during gastrulation and segmentation in the mouse embryo. Dev. Biol. 152, 75–88 (1992).

    Article  CAS  Google Scholar 

  40. Slack, J. M., Isaacs, H. V., Song, J., Durbin, L. & Pownall, M. E. The role of fibroblast growth factors in early Xenopus development. Biochem. Soc. Symp. 62, 1–12 (1996).

    CAS  PubMed  Google Scholar 

  41. Storey, K. G. et al. Early posterior neural tissue is induced by FGF in the chick embryo. Development 125, 473–484 (1998).

    CAS  PubMed  Google Scholar 

  42. Pownall, M. E., Tucker, A. S., Slack, J. M. & Isaacs, H. V. eFGF, Xcad3 and Hox genes form a molecular pathway that establishes the anteroposterior axis in Xenopus. Development 122, 3881–3892 (1996).

    CAS  PubMed  Google Scholar 

  43. Holowacz, T. & Sokol, S. FGF is required for posterior neural patterning but not for neural induction. Dev. Biol. 205, 296–308 (1999).

    Article  CAS  Google Scholar 

  44. Godsave, S. F. & Durston, A. J. Neural induction and patterning in embryos deficient in FGF signaling. Int. J. Dev. Biol. 41, 57–65 (1997).

    CAS  PubMed  Google Scholar 

  45. Koshida, S., Shinya, M., Mizuno, T., Kuroiwa, A. & Takeda, H. Initial anteroposterior pattern of the zebrafish central nervous system is determined by differential competence of the epiblast. Development 125, 1957–1966 (1998).

    CAS  PubMed  Google Scholar 

  46. Keller, R., Shih, J., Sater, A. K. & Moreno, C. Planar induction of convergence and extension of the neural plate by the organizer of Xenopus. Dev. Dyn. 193, 218–234 (1992).

    Article  CAS  Google Scholar 

  47. Yamada, T. Caudalization by the amphibian organizer: brachyury, convergent extension and retinoic acid. Development 120, 3051–3062 (1994).

    CAS  PubMed  Google Scholar 

  48. Yates, J. L., Warren, N. & Sugden, B. Stable replication of plasmids derived from Epstein–Barr virus in various mammalian cells. Nature 313, 812–815 (1985).

    Article  CAS  Google Scholar 

  49. Okada, A., Lansford, R., Weimann, J. M., Fraser, S. E. & McConnell, S. K. Imaging cells in the developing nervous system with retrovirus expressing modified green fluorescent protein. Exp. Neurol. 156, 394–406 (1999).

    Article  CAS  Google Scholar 

  50. Mombaerts, P. et al. Visualizing an olfactory sensory map. Cell 87, 675–686 (1996).

    Article  CAS  Google Scholar 

  51. Mathis, L., Sieur, J., Voiculescu, O., Charnay, P. & Nicolas, J. F. Successive patterns of clonal cell dispersion in relation to neuromeric subdivision in the mouse neuroepithelium. Development 126, 4095–4106 (1999).

    CAS  PubMed  Google Scholar 

  52. Kulesa, P. M. & Fraser, S. E. In ovo time-lapse analysis of chick hindbrain neural crest cell migration shows cell interactions during migration to the branchial arches. Development 127, 1161–1172 (2000).

    CAS  PubMed  Google Scholar 

  53. Kulesa, P. M. & Fraser, S. E. Neural crest cell dynamics revealed by time-lapse video microscopy. Dev. Biol. 15, 327–344 (1998).

    Article  Google Scholar 

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Acknowledgements

We thank R. Lansford, E. Dorman, E. Amaya and L. Niswander for reagents, M. Bronner-Fraser, M. Garcia-Castro, A. Knecht and H. McBride for comments on the manuscript, members of the Fraser laboratory for advice, and J. Horn for his help with electroporation. L.M. is the recipient of an EMBO long-term fellowship; P.M.K. is a participant in the California Institute of Technology Initiative in Computational Molecular Biology, which is funded by a Burroughs Wellcome Fund Interfaces award.

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Correspondence to Scott E. Fraser.

Supplementary information

Figure S1 Global displacement of mesoderm progenitors. (PDF 107 kb)

41556_2001_BFncb0601_559_MOESM2_ESM.qt

Movie 1 Elongation motion in Hensen's node region fated to the neurectoderm. Time-lapse analysis of the GFP population comprising the posterior neural plate and the node region. Frames are 5 min apart. Cell behaviours of this movie are summarized in Fig. 3a. (QT 1265 kb)

41556_2001_BFncb0601_559_MOESM3_ESM.qt

Movie 2 Coherent behaviour of neural progenitors. Two adjacent GFPexpressing cells retain their relative locations (coherence) during Hensen's node progression. (QT 2690 kb)

41556_2001_BFncb0601_559_MOESM4_ESM.qt

Movie 3 Elongation motion in Hensen's node region fated to the mesoderm. Clusters of axial (mesoderm) progenitors labelled by DiI become progressively displaced from each other while individual cells migrate away into the mesoderm. (QT 346 kb)

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Mathis, L., Kulesa, P. & Fraser, S. FGF receptor signalling is required to maintain neural progenitors during Hensen's node progression. Nat Cell Biol 3, 559–566 (2001). https://doi.org/10.1038/35078535

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