title: Directional cell migration, but not proliferation, drives hair placode morphogenesis.
abstract: Epithelial reorganization involves coordinated changes in cell shapes and movements. This restructuring occurs during formation of placodes, ectodermal thickenings that initiate the morphogenesis of epithelial organs including hair, mammary gland, and tooth. Signaling pathways in ectodermal placode formation are well known, but the cellular mechanisms have remained ill defined. We established imaging methodology for live visualization of embryonic skin explants during the first wave of hair placode formation. We found that the vast majority of placodal cells were nonproliferative throughout morphogenesis. We show that cell compaction and centripetal migration are the main cellular mechanisms associated with hair placode morphogenesis and that inhibition of actin remodeling suppresses placode formation. Stimulation of both ectodysplasin/NF-κB and Wnt/β-catenin signaling increased cell motility and the number of cells committed to placodal fate. Thus, cell fate choices and morphogenetic events are controlled by the same molecular pathways, providing the framework for coordination of these two processes.
authors.affiliation: Developmental Biology Program, Institute of Biotechnology, 00014 University of Helsinki, Helsinki, Finland. Electronic address: laura.ahtiainen@helsinki.fi.
authors.forename: Laura
authors.initials: L
authors.lastname: Ahtiainen
authors.affiliation: Developmental Biology Program, Institute of Biotechnology, 00014 University of Helsinki, Helsinki, Finland.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lefebvre
authors.affiliation: Developmental Biology Program, Institute of Biotechnology, 00014 University of Helsinki, Helsinki, Finland.
authors.forename: Päivi H
authors.initials: PH
authors.lastname: Lindfors
authors.affiliation: Developmental Biology Program, Institute of Biotechnology, 00014 University of Helsinki, Helsinki, Finland.
authors.forename: Elodie
authors.initials: E
authors.lastname: Renvoisé
authors.affiliation: Developmental Biology Program, Institute of Biotechnology, 00014 University of Helsinki, Helsinki, Finland.
authors.forename: Vera
authors.initials: V
authors.lastname: Shirokova
authors.affiliation: Cell and Molecular Biology Program, Institute of Biotechnology, 00014 University of Helsinki, Helsinki, Finland.
authors.forename: Maria K
authors.initials: MK
authors.lastname: Vartiainen
authors.affiliation: Developmental Biology Program, Institute of Biotechnology, 00014 University of Helsinki, Helsinki, Finland.
authors.forename: Irma
authors.initials: I
authors.lastname: Thesleff
authors.affiliation: Developmental Biology Program, Institute of Biotechnology, 00014 University of Helsinki, Helsinki, Finland. Electronic address: marja.mikkola@helsinki.fi.
authors.forename: Marja L
authors.initials: ML
authors.lastname: Mikkola
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D053331:Ectodysplasins / Q000502:physiology; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018859:Hair Follicle / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007633:Keratins / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009024:Morphogenesis / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495267:CTNNB1 protein, mouse; D053331:Ectodysplasins; C506019:Eda protein, mouse; C118917:Krt17 protein, mouse; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; D051153:Wnt Proteins; D051176:beta Catenin; D049452:Green Fluorescent Proteins; D007633:Keratins