title: Quantitative cell polarity imaging defines leader-to-follower transitions during collective migration and the key role of microtubule-dependent adherens junction formation.
abstract: The directed migration of cell collectives drives the formation of complex organ systems. A characteristic feature of many migrating collectives is a 'tissue-scale' polarity, whereby 'leader' cells at the edge of the tissue guide trailing 'followers' that become assembled into polarised epithelial tissues en route. Here, we combine quantitative imaging and perturbation approaches to investigate epithelial cell state transitions during collective migration and organogenesis, using the zebrafish lateral line primordium as an in vivo model. A readout of three-dimensional cell polarity, based on centrosomal-nucleus axes, allows the transition from migrating leaders to assembled followers to be quantitatively resolved for the first time in vivo. Using live reporters and a novel fluorescent protein timer approach, we investigate changes in cell-cell adhesion underlying this transition by monitoring cadherin receptor localisation and stability. This reveals that while cadherin 2 is expressed across the entire tissue, functional apical junctions are first assembled in the transition zone and become progressively more stable across the leader-follower axis of the tissue. Perturbation experiments demonstrate that the formation of these apical adherens junctions requires dynamic microtubules. However, once stabilised, adherens junction maintenance is microtubule independent. Combined, these data identify a mechanism for regulating leader-to-follower transitions within migrating collectives, based on the relocation and stabilisation of cadherins, and reveal a key role for dynamic microtubules in this process.
authors.affiliation: Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg 69117, Germany.
authors.forename: Céline
authors.initials: C
authors.lastname: Revenu
authors.forename: Sebastian
authors.initials: S
authors.lastname: Streichan
authors.forename: Erika
authors.initials: E
authors.lastname: Donà
authors.forename: Virginie
authors.initials: V
authors.lastname: Lecaudey
authors.forename: Lars
authors.initials: L
authors.lastname: Hufnagel
authors.forename: Darren
authors.initials: D
authors.lastname: Gilmour
mesh_terms: D022005:Adherens Junctions / Q000235:genetics / Q000502:physiology; D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D053403:Lateral Line System / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D008870:Microtubules / Q000235:genetics / Q000502:physiology; D038081:Organogenesis / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D011994:Recombinant Proteins; D029961:Zebrafish Proteins; D049452:Green Fluorescent Proteins
keywords: Cell adhesion; Collective migration; Lateral line; Microtubules; Morphogenesis; Zebrafish