Amelogenin in cranio‐facial development: the tooth as a model to study the role of amelogenin during embryogenesis

Abstract

The amelogenins comprise 90% of the developing extracellular enamel matrix proteins and play a major role in the biomineralization and structural organization of enamel. Amelogenins were also detected, in smaller amounts, in postnatal calcifying mesenchymal tissues, and in several nonmineralizing tissues including brain. Low molecular mass amelogenin isoforms were suggested to have signaling activity; to produce ectopically chondrogenic and osteogenic‐like tissue and to affect mouse tooth germ differentiation in vitro. Recently, some amelogenin isoforms were found to bind to the cell surface receptors; LAMP‐1, LAMP‐2 and CD63, and subsequently localize to the perinuclear region of the cell. The recombinant amelogenin protein (rHAM+) alone brought about regeneration of the tooth supporting tissues: cementum, periodontal ligament and alveolar bone, in the dog model, through recruitment of progenitor cells and mesenchymal stem cells.We show that amelogenin is expressed in various tissues of the developing mouse embryonic cranio‐facial complex such as brain, eye, ganglia, peripheral nerve trunks, cartilage and bone, and is already expressed at E10.5 in the brain and eye, long before the initiation of tooth formation. Amelogenin protein expression was detected in the tooth germ (dental lamina) already at E13.5, much earlier than previously reported (E19). Application of amelogenin (rHAM+) beads together with DiI, on E13.5 and E14.5 embryonic mandibular mesenchyme and on embryonic tooth germ, revealed recruitment of mesenchymal cells. The present results indicate that amelogenin has an important role in many tissues of the cranio‐facial complex during mouse embryonic development and differentiation, and might be a multifunctional protein. J. Exp. Zool. (Mol. Dev. Evol.) 312B:445–457, 2009. © 2008 Wiley‐Liss, Inc.

Tracking Endogenous Amelogenin and Ameloblastin In Vivo

“…In line with previous studies [15], [16], repeated or occasional mRNA expression of AMBN and AMELX was detected in several soft tissues but at low level when compared to mandibular tissues. This occasional expression could result from endogenous oscillations of EMPs gene expression orchestrated by clock genes; both AMELX and enamelin being downstream targets of the “clock genes” family of transcription factors [37], [38].…”

Intrinsically Disordered Proteins in Biomineralization

“…They are abundant in tooth enamel, but amelogenin has also been identified in dentin, bone, cartilage and nonmineralizing tissues such as those of the brain, salivary glands and macrophages (Gruenbaum-Cohen et al, 2009;Lyngstadaas et al, 2009). Amelogenin is involved in biomineralization as well as cell signaling events (Gruenbaum-Cohen et al, 2009;Lyngstadaas et al, 2009;Veis, 2003).…”

“…Proteins involved in biomineralization have to bind many targets to properly fulfill their functions. They are responsible for macromolecular complex assembly, and they are engaged in cell attachment (Fujisawa et al, 1997;Stubbs et al, 1997), cell signaling (Gruenbaum-Cohen et al, 2009) and/or the regulation of gene expression (Narayanan et al, 2003(Narayanan et al, , 2006. Macromolecular complex assemblies are crucial for proper biomineral formation.…”

Enamel Protein Regulation and Dental and Periodontal Physiopathology in Msx2 Mutant Mice

“…27 Besides their role as structural proteins, amelogenin and ameloblastin isoforms are proposed to play a role in cell signaling. 28 Amelogenin peptides were shown to induce bone-cell differentiation via Runx-2 pathway activation in vivo and in vitro. 29,30 Amelogenin null mutants show regional hyperesorption mediated by activation of RANKL-RANK pathway.…”