title: Luminal signalling links cell communication to tissue architecture during organogenesis.
abstract: Morphogenesis is the process whereby cell collectives are shaped into differentiated tissues and organs. The self-organizing nature of morphogenesis has been recently demonstrated by studies showing that stem cells in three-dimensional culture can generate complex organoids, such as mini-guts, optic-cups and even mini-brains. To achieve this, cell collectives must regulate the activity of secreted signalling molecules that control cell differentiation, presumably through the self-assembly of microenvironments or niches. However, mechanisms that allow changes in tissue architecture to feedback directly on the activity of extracellular signals have not been described. Here we investigate how the process of tissue assembly controls signalling activity during organogenesis in vivo, using the migrating zebrafish lateral line primordium. We show that fibroblast growth factor (FGF) activity within the tissue controls the frequency at which it deposits rosette-like mechanosensory organs. Live imaging reveals that FGF becomes specifically concentrated in microluminal structures that assemble at the centre of these organs and spatially constrain its signalling activity. Genetic inhibition of microlumen assembly and laser micropuncture experiments demonstrate that microlumina increase signalling responses in participating cells, thus allowing FGF to coordinate the migratory behaviour of cell groups at the tissue rear. As the formation of a central lumen is a self-organizing property of many cell types, such as epithelia and embryonic stem cells, luminal signalling provides a potentially general mechanism to locally restrict, coordinate and enhance cell communication within tissues.
authors.affiliation: European Molecular Biology Laboratory Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Sevi
authors.initials: S
authors.lastname: Durdu
authors.affiliation: European Molecular Biology Laboratory Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Murat
authors.initials: M
authors.lastname: Iskar
authors.affiliation: European Molecular Biology Laboratory Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Celine
authors.initials: C
authors.lastname: Revenu
authors.affiliation: European Molecular Biology Laboratory Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schieber
authors.affiliation: European Molecular Biology Laboratory Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kunze
authors.affiliation: European Molecular Biology Laboratory Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Peer
authors.initials: P
authors.lastname: Bork
authors.affiliation: European Molecular Biology Laboratory Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Schwab
authors.affiliation: European Molecular Biology Laboratory Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Darren
authors.initials: D
authors.lastname: Gilmour
mesh_terms: D000818:Animals; D002450:Cell Communication; D002454:Cell Differentiation; D002465:Cell Movement; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism; D038081:Organogenesis; D015398:Signal Transduction; D013997:Time Factors; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism
chemical_list: D005346:Fibroblast Growth Factors