Role of Cell Death in Cellular Processes During Odontogenesis

Abstract

The development of a tooth germ in a precise size, shape, and position in the jaw, involves meticulous regulation of cell proliferation and cell death. Apoptosis, as the most common type of programmed cell death during embryonic development, plays a number of key roles during odontogenesis, ranging from the budding of the oral epithelium during tooth initiation, to later tooth germ morphogenesis and removal of enamel knot signaling center. Here, we summarize recent knowledge about the distribution and function of apoptotic cells during odontogenesis in several vertebrate lineages, with a special focus on amniotes (mammals and reptiles). We discuss the regulatory roles that apoptosis plays on various cellular processes during odontogenesis. We also review apoptosis-associated molecular signaling during tooth development, including its relationship with the autophagic pathway. Lastly, we cover apoptotic pathway disruption, and alterations in apoptotic cell distribution in transgenic mouse models. These studies foster a deeper understanding how apoptotic cells affect cellular processes during normal odontogenesis, and how they contribute to dental disorders, which could lead to new avenues of treatment in the future.

Important roles of odontoblast membrane phospholipids in early dentin mineralization

“…41 Previous reports have also identified odontoblast apoptosis during odontogenesis. 42–44 However, these studies have identified cell apoptosis in stages before initial mineralization, i.e. , at E12–E13, and have associated the cell fate with molecular signaling including the autophagic pathway.…”

“…41 Previous reports have also identified odontoblast apoptosis during odontogenesis. [42][43][44] However, these studies have identified cell apoptosis in stages before initial mineralization, i.e., at E12-E13, and have associated the cell fate with molecular signaling including the autophagic pathway. 42,43 On the other hand, our results indicated the involvement of cell membrane components, identified by annexin V immunostaining, as initiators of early dentin mineralization.…”

“…[42][43][44] However, these studies have identified cell apoptosis in stages before initial mineralization, i.e., at E12-E13, and have associated the cell fate with molecular signaling including the autophagic pathway. 42,43 On the other hand, our results indicated the involvement of cell membrane components, identified by annexin V immunostaining, as initiators of early dentin mineralization.…”

Tooth number abnormality: from bench to bedside

“…51 IK is silenced via apoptosis at the bud stage. 5,52 IK with specific Eda and NFkB signalling was originally observed in the incisors, and its size affects the incisor germ size. 53 The molar IK has high expression of Wnt and Shh, and interference of IK formation via physical ablation or Wnt signal confusion can prevent the development of the tooth germ.…”

The effects of 4-Phenylbutyric acid on ER stress during mouse tooth development

“…Interactions between epithelium and the underlying mesenchyme play important roles for development of tooth from bud, cap, bell to secretory stages ( Santosh and Jones, 2014 ; Balic, 2018 ). At cap stage, enamel knot (EK), a non-proliferating signaling center of tooth development closely linked with epithelial-mesenchymal interactions, expresses important signaling molecules including autocrine and paracrine factors, and transcription factors for proper tooth morphogenesis ( Yu and Klein, 2020 ; Abramyan et al, 2021 ). At the secretory stage, inner enamel epithelium (IEE) begins differentiate into ameloblasts and the underlying mesenchymal dental papilla (DP) differentiate into odontoblasts for the secretion of enamel and dentin respectively ( Otsu et al, 2011 ; Kawashima and Okiji, 2016 ).…”