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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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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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