MAST4 regulates stem cell maintenance with DLX3 for epithelial development and amelogenesis

Abstract

The asymmetric division of stem cells permits the maintenance of the cell population and differentiation for harmonious progress. Developing mouse incisors allows inspection of the role of the stem cell niche to provide specific insights into essential developmental phases. Microtubule-associated serine/threonine kinase family member 4 (Mast4) knockout (KO) mice showed abnormal incisor development with low hardness, as the size of the apical bud was decreased and preameloblasts were shifted to the apical side, resulting in amelogenesis imperfecta. In addition, Mast4 KO incisors showed abnormal enamel maturation, and stem cell maintenance was inhibited as amelogenesis was accelerated with Wnt signal downregulation. Distal-Less Homeobox 3 (DLX3), a critical factor in tooth amelogenesis, is considered to be responsible for the development of amelogenesis imperfecta in humans. MAST4 directly binds to DLX3 and induces phosphorylation at three residues within the nuclear localization site (NLS) that promotes the nuclear translocation of DLX3. MAST4-mediated phosphorylation of DLX3 ultimately controls the transcription of DLX3 target genes, which are carbonic anhydrase and ion transporter genes involved in the pH regulation process during ameloblast maturation. Taken together, our data reveal a novel role for MAST4 as a critical regulator of the entire amelogenesis process through its control of Wnt signaling and DLX3 transcriptional activity. The research examines the function of MAST4, a protein, in tooth growth, particularly in creating enamel (the hard, outer layer of the tooth). Scientists discovered that mice without MAST4 had unusual enamel development in their front teeth, resulting in weaker teeth. The research showed that MAST4 is vital for preserving stem cells (cells that can develop into many different cell types) and controlling their transformation into ameloblasts (cells that create enamel). Without MAST4, this process was disrupted, causing early enamel release and incorrect maturation. The scientists also discovered that MAST4 controls the function of another protein, DLX3, necessary for enamel maturation. This research offers a new understanding of the molecular processes involved in tooth growth and could be significant for understanding and treating dental issues. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.