Dpp signaling directs cell motility and invasiveness during epithelial morphogenesis.
Tissue remodeling in development and disease involves the coordinated invasion of neighboring territories and/or the replacement of entire cell populations. Cell guidance, cell matching, transitions from passive to migratory epithelia, cell growth and death, and extracellular matrix remodeling all impinge on epithelial spreading. Significantly, the extracellular signals that direct these activities and the specific cellular elements and mechanisms regulated by these signals remain in most cases to be identified. To address these issues, we performed an analysis of histoblasts (Drosophila abdominal epithelial founder cells) on their transition from a dormant state to active migration replacing obsolete larval epidermal cells (LECs). We found that during expansion, Decapentaplegic (Dpp) secreted from surrounding LECs leads to graded pathway activation in cells at the periphery of histoblast nests. Across nests, Dpp activity confers differential cellular behavior and motility by modulating cell-cell contacts, the organization and activity of the cytoskeleton, and histoblast attachment to the substrate. Furthermore, Dpp also prevents the premature death of LECs, allowing the coordination of histoblast expansion to LEC delamination. Dpp signaling activity directing histoblast spreading and invasiveness mimics transforming growth factor-beta and bone morphogenetic proteins' role in enhancing the motility and invasiveness of cancer cells, resulting in the promotion of metastasis.
Instituto de Biología Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Parc Científic de Barcelona, Baldiri Reixac 10, 08028 Barcelona, Spain.
Nikolay
N
Ninov
Sofia
S
Menezes-Cabral
Carla
C
Prat-Rojo
Cristina
C
Manjón
Alexander
A
Weiss
George
G
Pyrowolakis
Markus
M
Affolter
Enrique
E
Martín-Blanco
D000199:Actins / Q000502:physiology; D000818:Animals; D030801:Animals, Genetically Modified; D019898:Autocrine Communication; D001483:Base Sequence; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D004330:Drosophila / Q000235:genetics / Q000254:growth & development* / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D004848:Epithelium / Q000254:growth & development; D049452:Green Fluorescent Proteins / Q000235:genetics; D007814:Larva / Q000166:cytology / Q000254:growth & development; D009024:Morphogenesis; D019899:Paracrine Communication; D011994:Recombinant Proteins / Q000235:genetics; D015398:Signal Transduction
D000199:Actins; D017931:DNA Primers; D029721:Drosophila Proteins; D011994:Recombinant Proteins; C064196:dpp protein, Drosophila; D049452:Green Fluorescent Proteins