Early evolution of enamel matrix proteins is reflected by pleiotropy of physiological functions

Abstract

Highly specialized enamel matrix proteins (EMPs) are predominantly expressed in odontogenic tissues and diverged from common ancestral gene. They are crucial for the maturation of enamel and its extreme complexity in multiple independent lineages. However, divergence of EMPs occured already before the true enamel evolved and their conservancy in toothless species suggests that non-canonical functions are still under natural selection. To elucidate this hypothesis, we carried out an unbiased, comprehensive phenotyping and employed data from the International Mouse Phenotyping Consortium to show functional pleiotropy of amelogenin, ameloblastin, amelotin, and enamelin, genes, i.e. in sensory function, skeletal morphology, cardiovascular function, metabolism, immune system screen, behavior, reproduction, and respiratory function. Mice in all KO mutant lines, i.e. amelogenin KO, ameloblastin KO, amelotin KO, and enamelin KO, as well as mice from the lineage with monomeric form of ameloblastin were affected in multiple physiological systems. Evolutionary conserved motifs and functional pleiotropy support the hypothesis of role of EMPs as general physiological regulators. These findings illustrate how their non-canonical function can still effect the fitness of modern species by an example of influence of amelogenin and ameloblastin on the bone physiology.

Semi‐Automated MicroCT Analysis of Bone Anatomy and Mineralization in Mouse Models

“…The ability to obtain an overview of the anatomy and mineralization of the skeletal system is important to understanding bone development, diseases, and potential treatments (Benova et al., 2023; Gewartowska et al., 2021; Kralova et al., 2020; Spoutil et al., 2023). In this area of research, mouse models have emerged as highly advantageous tools that enable exploration of diverse conditions and unveil underlying pathophysiological mechanisms and therapeutic prospects (Beamer et al., 1999; Jepsen et al., 2015; Saless et al., 2011).…”