Amelogenesis is the formation of enamel. An enamel is formed by Ameloblasts. In our body, all types of mineralized tissues have two components, organic matter and mineralized inorganic matter. Always the organic matter is deposited first which forms a basic structure, on which mineralization occurs. So amelogenesis also takes place in two stages, first organic matrix formation and then mineralization of that organic matrix. The fully formed enamel is 96% mineralized and has only 4% organic matter. In the life cycle of Ameloblast, Amelogenesis occurs in Formative stage and Maturative stage. The whole of organic matrix formation occurs in the Formative stage, however the mineralization occurs in two phases. Phase one occurs in the Formative stage where 25 to 30% mineralization occurs and phase 2 occurs in the Maturative stage, where the rest 70-75% mineralization occurs. Let us start with the formation of the organic matrix. During tooth development when enamel organ enters the Advanced bell stage, Odontoblast starts depositing dentin and sends signal to Ameloblast to start Amelogenesis and enter the Formative stage. The tall columnar Ameloblasts develop a pyramidal process on the distal surface called Tomes process. An incomplete septa separates them partially from the cell proper called Distal terminal bars. The Ameloblast now start depositing the organic matter. The organic matter of enamel has no collagenous proteins in it. Instead it is formed of enamel proteins, which are classified as Amelogenins and Non-Amelogenins. The Amelogenins are the main proteins constituting 90%, whereas Non-Amelogenins form only 10% of the organic matter. They include Ameloblastin and Enamelin. All these enamel proteins form the framework on which mineralization will take place. As Ameloblasts deposit enamel, they continuously keep moving in the opposite direction. By the end of the Formative stage the whole thickness of enamel is formed constituting all of the organic matter. Now coming to mineralization. The main inorganic portion of enamel is formed by the hydroxyapatite crystals. As we just saw, the complete organic matter formation occurs in just one phase, during the Formative stage. However, mineralization occurs in two phases about 25 to 30% during the Formative stage, along with the organic matrix formation. It is also referred to as 'immediate partial mineralization', and the rest 75% during the Maturative stage. Let us see the first phase of mineralization which occurs during the Formative stage. In the Formative stage the Ameloblasts have Tomes processes which have a non-secreting side and a secreting side. The secreting side has two parts, distal part and proximal part. From the distal part, hydroxyapatite crystals are released parallel to the long axis of the enamel rods. Whereas from the proximal part hydroxyapatite crystals are released at 65 degrees to the long axis and form the inter-rod. These crystals are at a distance from each other as enamel proteins are present in between. If we study the relationship between Ameloblast and enamel rod, each Ameloblast contributes to the formation of 4 enamel rods and each enamel rod is formed by the contribution of 4 Ameloblasts. By the end of Formative stage the complete organic matrix secretion and first step of mineralization are done. That is, complete width of enamel is formed and it is the mixture of enamel proteins and 30% of mineralization. Now the second phase of mineralization which occurs in the Maturative stage of Ameloblast. During the Maturative stage the Ameloblasts lose their Tome's processes. The distal surface now alternately interchanges between being ruffled and smooth. This interchange is called 'modulation'. In this phase, the Ameloblasts have one job to do, that is to increase the enamel mineralization to the final goal of 96%. No new hydroxyapatite crystals are released. Ameloblasts secrete minerals which get deposited on the already present hydroxyapatite crystals and cause their gradual increase in size. As the crystals increase in size they squeeze the enamel proteins out, towards the Ameloblasts where they are absorbed. Now for easy and quick reabsorption of enamel proteins, Ameloblasts release enzymes, like Enamelysin and Kallikrien4. These enzymes degrade the enamel proteins into smaller fragments and absorb them easily. That is why, the second phase of mineralization occurs first near the Dentino-enamel junction, then moves towards the outer surface, continuously pushing the enamel proteins back where they came from. As mineralization proceeds the percentage of minerals in the enamel increases and reaches its goal of 96%. Whereas, only 4% organic matter is left behind. If we study the formation of all calcified tissues of the body, we see that Amelogenesis is unique. Let us see how. All mineralized tissues in the body are formed by cells which are of connective tissue origin. Only enamel is formed by cells which are epithelial in origin. Additionally, the forming cells of all mineralized tissues in the body are present to continuously create the tissues lifelong. Only in Amelogenesis, after the complete formation of enamel, the Ameloblasts get destroyed, so that no repair or renewal of enamel can be done later in life. All mineralized tissues in the body have their organic matter formed of collagen proteins, only enamel has no collagen. It has other proteins specifically called Enamel proteins. All mineralized tissues in the body, during their formation, have a layer which is completely unmineralized. Only in Amelogenesis no such stage is present. The organic portion shows immediate partial mineralization of 30% from the very beginning. Finally, in all mineralized tissues of the body, once organic matter is secreted it is not reabsorbed. Only in Amelogenesis the enamel proteins after secretion are absorbed back.