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Social interactions among epithelial cells during tracheal branching morphogenesis

Naturevolume 441pages746749 (2006) | Download Citation

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Abstract

Many organs are composed of tubular networks that arise by branching morphogenesis in which cells bud from an epithelium and organize into a tube1,2,3. Fibroblast growth factors (FGFs) and other signalling molecules have been shown to guide branch budding and outgrowth4,5,6,7, but it is not known how epithelial cells coordinate their movements and morphogenesis. Here we use genetic mosaic analysis in Drosophila melanogaster to show that there are two functionally distinct classes of cells in budding tracheal branches: cells at the tip that respond directly to Branchless FGF and lead branch outgrowth, and trailing cells that receive a secondary signal to follow the lead cells and form a tube. These roles are not pre-specified; rather, there is competition between cells such that those with the highest FGF receptor activity take the lead positions, whereas those with less FGF receptor activity assume subsidiary positions and form the branch stalk. Competition appears to involve Notch-mediated lateral inhibition that prevents extra cells from assuming the lead. There may also be cooperation between budding cells, because in a mosaic epithelium, cells that cannot respond to the chemoattractant, or respond only poorly, allow other cells in the epithelium to move ahead of them.

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Acknowledgements

We thank B. Levi for help with isolation of ‘no mutant terminal cell’ mutants and for discussion, and S. Artavanis, M. Galko, S. Luschnig and S. Toering for fly stocks and antisera. This work was supported by an NIH NRSA fellowship (A.S.G.) and a grant from the N.I.H. M.A.K. is an investigator of the Howard Hughes Medical Institute. Author Contributions A.S.G. conceived, designed and performed experiments and analysed data. M.A.K. advised on the above. A.S.G. and M.A.K. wrote the paper.

Author information

Affiliations

  1. Howard Hughes Medical Institute, Department of Biochemistry, Stanford University School of Medicine, Stanford, California, 94305-5307, USA

    • Amin S. Ghabrial
    •  & Mark A. Krasnow

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Competing interests

Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

Corresponding author

Correspondence to Mark A. Krasnow.

Supplementary information

  1. Supplementary Methods

    This file contains additional details of the methods used in this study. (DOC 8 kb)

  2. Supplementary Table 1

    Distribution of positively-marked cell clones in mosaic dorsal branches. (DOC 10 kb)

  3. Supplementary Table 2

    Distribution of control tracheal clones (btl+/+) in wild-type (btl+/+) animals. Each row represents the structure of a mosaic DB of the genotype indicated in the title of the table, and each cell in a row describes the tracheal cell at that position in the DB. (DOC 591 kb)

  4. Supplementary Table 3

    Distribution of btl724/724 tracheal clones in heterozygous (btl+/724) animals. Each row represents the structure of a mosaic DB of the genotype indicated in the title of the table, and each cell in a row describes the tracheal cell at that position in the DB. (DOC 334 kb)

  5. Supplementary Table 4

    Distribution of btl788/788 tracheal clones in heterozygyous (btl+/788) animals. Each row represents the structure of a mosaic DB of the genotype indicated in the title of the table, and each cell in a row describes the tracheal cell at that position in the DB. (DOC 351 kb)

  6. Supplementary Table 5

    Distribution of pntΔ88/Δ88 tracheal clones in heterozygous (pnt+/Δ88) animals. Each row represents the structure of a mosaic DB of the genotype indicated in the title of the table, and each cell in a row describes the tracheal cell at that position in the DB. (DOC 311 kb)

  7. Supplementary Table 6

    Distribution of btlBN/BN tracheal clones in heterozygous (btl+/BN) animals. Each row represents the structure of a mosaic DB of the genotype indicated in the title of the table, and each cell in a row describes the tracheal cell at that position in the DB. (DOC 420 kb)

  8. Supplementary Table 7

    Distribution of wild-type (btl+/+) tracheal clones in heterozygous (btl+/788) animals. Each row represents the structure of a mosaic DB of the genotype indicated in the title of the table, and each cell in a row describes the tracheal cell at that position in the DB. (DOC 450 kb)

  9. Supplementary Table 8

    Distribution of wild-type (btl+/+) tracheal clones in heterozygous (btl+/1187) animals. Each row represents the structure of a mosaic DB of the genotype indicated in the title of the table, and each cell in a row describes the tracheal cell at that position in the DB. (DOC 431 kb)

  10. Supplementary Table 9

    Distribution of spryΔ5/Δ5 tracheal clones in heterozygous (spry+/Δ5) animals. Each row represents the structure of a mosaic DB of the genotype indicated in the title of the table, and each cell in a row describes the tracheal cell at that position in the DB. (DOC 346 kb)

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https://doi.org/10.1038/nature04829

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