Articles reveal the cellular choreography that creates teeth, hair follicles and mammary glands during development in the womb
Professor Jeremy Green from King’s College London’s Dental Institute has published two articles that show for the first time how cell rearrangements create the grooves and pits required to build teeth, hair follicles and mammary ducts. The work revealed the different cellular manoeuvres and showed that they rely on distinct genetic pathways. The first paper investigates the creation of the tooth bud and the mechanisms driving stratification and invagination. The second papers looks at the invagination process in detail, and the migration of cells. Both represent part of a new era in developmental biology (embryology) that investigates how genes control cells to make tissues in the body. This goes beyond knowing the “parts list” of genes in the genome and towards understanding the physical creation of tissues and organs. “It’s a kind of biological origami – tissues in the embryo must fold themselves into the structures that we see at birth”, said Professor Green. He added: “This is at the core of understanding how birth defects happen, and how we may one day be able to repair them with stem cells.”
Paper abstracts and summaries:
Epithelial stratification and placode invagination are separable functions in early morphogenesis of the molar tooth
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-offunction 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.
Invagination of Ectodermal Placodes Is Driven by Cell Intercalation-Mediated Contraction of the Suprabasal Tissue Canopy
Teeth, hair follicles, and skin ducts (including mammary and sweat glands) are initially formed in the embryo as slight thickenings of a flat epithelium that are called placodes. These then invaginate to form dimples or pits that make the characteristic structures found in the adult. While some invagination mechanisms are well-studied and it is recognized that invagination is one of the basic motifs needed to construct the body, the physical events that lead placodes to invaginate are unclear. Here, we analyzed the events required to form tooth placodes and identified a novel mechanism: we showed that the superficial layer of the placode contracts to pucker the underlying epithelium, ultimately forcing it deep into the underlying mesenchyme. We demonstrated that the superficial tissue generates contractile forces and that the mechanical tension deforms nuclei in this tissue. This allowed us to map the tension not only in developing teeth, but also in hair follicles and mammary glands, revealing similar patterns of nuclear distortion in different tissues and suggesting the existence of a shared mechanism of invagination. We also labelled individual cells and tracked them in real time, showing that the tissue contracts via cell intercalation, with some cells remaining anchored to the basal layer of the epithelium while trying to migrate toward the placode centre. Overall, our results describe the dynamic rearrangements that take place during tooth placode formation and suggest that similar processes occur in other organs that are formed by invagination of stratified placodes.
Notes to editors
For more information please contact Laura Shepherd, Senior Communications Officer at the King’s College London Dental Institute on +44 (0) 027 188 1163, or laura.2.shepherd@kcl.ac.uk
Jeremy Green is a Professor of Developmental Biology in the Craniofacial Development and Stem Cell Biology Division of the Dental Institute at King’s College London.
“Epithelial stratification and placode invagination are separable functions in early morphogenesis of the molar tooth” by Jingjing Li, Lemonia Chatzeli, Eleni Panousopoulou, Abigail S. Tucker and Jeremy B. A. Green was published by The Company of Biologists Ltd on 11 January, 2016 and can be accessed here: http://www.ncbi.nlm.nih.gov/pubmed/26755699
“Invagination of Ectodermal Placodes Is Driven by Cell Intercalation-Mediated Contraction of the Suprabasal Tissue Canopy” by Eleni Panousopoulou, Jeremy B. A. Green was published in PLOS Biology on March 9, 2016 and can be accessed here: http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1002405
About King’s College London
King's College London is one of the top 20 universities in the world (2015/16 QS World University Rankings) and the fourth oldest in England. It is The Sunday Times 'Best University for Graduate Employment 2012/13'. King's has nearly 26,000 students (of whom more than 10,600 are graduate students) from some 140 countries worldwide, and more than 7,000 staff.