title: Epithelial stratification and placode invagination are separable functions in early morphogenesis of the molar tooth.
abstract: Ectodermal organs, which include teeth, hair follicles, mammary ducts, and glands such as sweat, mucous and sebaceous glands, are initiated in development as placodes, which are epithelial thickenings that invaginate and bud into the underlying mesenchyme. These placodes are stratified into a basal and several suprabasal layers of cells. The mechanisms driving stratification and invagination are poorly understood. Using the mouse molar tooth as a model for ectodermal organ morphogenesis, we show here that vertical, stratifying cell divisions are enriched in the forming placode and that stratification is cell division dependent. Using inhibitor and gain-of-function experiments, we show that FGF signalling is necessary and sufficient for stratification but not invagination as such. We show that, instead, Shh signalling is necessary for, and promotes, invagination once suprabasal tissue is generated. Shh-dependent suprabasal cell shape suggests convergent migration and intercalation, potentially accounting for post-stratification placode invagination to bud stage. We present a model in which FGF generates suprabasal tissue by asymmetric cell division, while Shh triggers cell rearrangement in this tissue to drive invagination all the way to bud formation.
authors.affiliation: Department of Craniofacial Development & Stem Cell Biology, King's College London, London SE1 9RT, UK.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Craniofacial Development & Stem Cell Biology, King's College London, London SE1 9RT, UK.
authors.forename: Lemonia
authors.initials: L
authors.lastname: Chatzeli
authors.affiliation: Department of Craniofacial Development & Stem Cell Biology, King's College London, London SE1 9RT, UK.
authors.forename: Eleni
authors.initials: E
authors.lastname: Panousopoulou
authors.affiliation: Department of Craniofacial Development & Stem Cell Biology, King's College London, London SE1 9RT, UK.
authors.forename: Abigail S
authors.initials: AS
authors.lastname: Tucker
authors.affiliation: Department of Craniofacial Development & Stem Cell Biology, King's College London, London SE1 9RT, UK jeremy.green@kcl.ac.uk.
authors.forename: Jeremy B A
authors.initials: JB
authors.lastname: Green
mesh_terms: D000818:Animals; D002455:Cell Division; D049109:Cell Proliferation; D004848:Epithelium / Q000196:embryology*; D005346:Fibroblast Growth Factors / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D008963:Molar / Q000166:cytology / Q000196:embryology*; D009024:Morphogenesis; D009929:Organ Size; D015398:Signal Transduction; D008941:Spindle Apparatus
chemical_list: D053823:Hedgehog Proteins; C465570:Shh protein, mouse; D005346:Fibroblast Growth Factors
keywords: Asymmetric cell division; Ectodermal organ; Invagination; Morphogenesis; Placode