Imaging Cellular Mechanisms of Oral Ectodermal Development and Disease

Forskningsoutput: AvhandlingDoktorsavhandlingSamling av artiklar

Sammanfattning

Specialized signaling centers act as organizers of embryonic morphogenesis. In the mammalian molar tooth, reiterative signaling in specialized centers called the enamel knots (EKs) determine tooth number, size, and shape. The tooth initiating placode and later primary EK signaling center share molecular markers, but it was not clear what the relationship between these two is and what cellular behaviors are contributing to early molar morphogenesis. In this thesis work, I used molecular tools and fluorescent reporter mouse models to visualize cellular behaviors with confocal microscopy of intact live and fixed tissues on a single cell level.

I uncovered that the molar is regulated by an initiation knot (IK) signaling center prior to the EKs. The molar IK arises in the placode: cells exit the cell cycle, condense via migration and drive proliferation in the bud. The IK is apoptotically silenced as the primary EK arises independently. I verified that the IK is an early signaling center belonging to the molar itself and argue that it plays a fundamental role in establishing the tooth fields and defining tooth shape. I also explored the mechanisms of signaling center dysregulation in tooth dysplasia models lacking the transcription factor Forkhead box i3 (Foxi3). Foxi3 placode and bud stage mutants revealed abnormal cell behaviors including signaling center fate definition, cell cycle regulation abnormalities and signaling center longevity. These changes result in arrest of tooth morphogenesis and abnormal tooth shape. Lastly, I reviewed the different experimental setups used to study tooth development with imaging approaches. I concluded that the continual advancement of imaging technologies is shedding light on the fundamental mechanisms of tooth development, especially during the earliest stages.
Originalspråkengelska
Tilldelande institution
  • Helsingfors universitet
Handledare
  • Ahtiainen, Laura, Handledare
  • Moustakas-Verho, Jacqueline Emmanuel, Handledare
Tilldelningsdatum20 nov. 2022
Förlag
Tryckta ISBN978-951-51-8463-4
Elektroniska ISBN978-951-51-8464-1
StatusPublicerad - 12 sep. 2022
MoE-publikationstypG5 Doktorsavhandling (artikel)

Vetenskapsgrenar

  • 119 Övrig naturvetenskap

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