Comparative PCR array analysis has shown an increased statistical significance (14-fold) in the expression levels between E13.0 and E15.0 [67]. functions and highlighting the crosstalk between FGFs and other signaling pathways. 1. Introduction Organogenesis is a complex physiological process. An intricate array of signaling molecules such as FGFs, bone morphogenetic proteins (BMPs), Wnt, and Hedgehog (Hh) families are known to regulate the formation, differentiation, and maintenance of the tooth and alveolar bone during the development and throughout adulthood [1C4]. FGF signaling occupies a significant position in inducing the proliferation and differentiation of multiple cell types during embryonic stages [5C10], as well as in regulating the development in different animals [11C14]. In addition, FGFs have been shown to regulate mouse tooth development [2, 15C17]. Nevertheless, a comprehensive description about the mechanism underlying FGFs that regulate different mineralized tissues of tooth during the embryonic stages, as well as incisor renewal in the adulthood, is still needed. Here, we summarize the roles of FGF signaling in mouse tooth development and the ways FGFs control the stem cells in incisor renewal, trying to separate its different functions and highlighting the crosstalk between FGFs and other signaling pathways. 2. Development of Tooth and Supporting Bone Structure Most vertebrate groups have the ability to replace their teeth. Mammals have two sets of teeth: primary and adult teeth. In contrast, mice contain one set with two different types: molars located at the proximal area and incisor located at the distal area, which are separated by the toothless diastema region. Mouse incisors grow continuously throughout the lifetime in sharp contrast to the molars. It has been demonstrated that the presence of stem cells, which are located in the proximal end of the incisor, gives rise to the differentiated tooth cell types, thus promoting continuous growth of this tooth [18]. It has been widely held that tooth morphogenesis is characterized by the sequential interactions between the mesenchymal cells derived from the cranial neural crest, and the stomadial epithelium [19, 20]. This process consists of several phases, that is, bud, cap, and bell stages. In mice, the dental mesenchyme is attributed to neural crest cells which are derived from the midbrain and hindbrain regions around embryonic day 8.5 (E8.5) [21C24]. The determination of tooth-forming sites during E10.5 [25C27] and the thickening of the dental epithelium at E11.5 have been considered as the first signs of tooth development [28]. During the bud stage (E12.5CE13.5), in both incisor and molar, the thickened dental epithelium buds into the underlying mesenchyme, thus forming the epithelial tooth bud around the condensed mesenchymal cells. At the subsequent cap stage (E14.5CE15.5), the epithelial component undergoes specific folding. A central event, during the transitional process between bud and cap stages, is the formation of the enamel knot (EK), a structure composed of a group of nondividing cells. Moreover, several signaling molecules, such as Shh, FGF4, FGF9, BMP4, and BMP7, as well as Wnt10a/b, are restrictedly expressed in the enamel knot. Several studies have shown that the EK, as the signaling center, has an important role in tooth cusp patterning control [29, 30]. During the following bell stage, the ameloblasts and odontoblasts originate from the dental 4-Chloro-DL-phenylalanine epithelium and mesenchyme, respectively [2]. At this stage, the secondary EKs (sEK) succeed the primary EKs (pEK) in the molar. In addition, the condensed mesenchymal cells around the developing epithelial tooth germ at the bud stage go on to differentiate into a supporting alveolar bone that forms the sockets for the teeth at the bell stage [31C33]. With reference to its origin, it has been reported that the alveolar bone is formed by intramembranous ossification [32, 33]. Intramembranous ossification starts with the mesenchymal cells which are derived from embryonic lineages correspondingly, which then migrate towards the locations of the future bones. Here, they form high cellular density condensations that outline the size and shape of the future bones. The mesenchymal cells subsequently differentiate.In tooth cultures, exogenous FGF2 and FGF4 promote the expression level of decreases in mice [90]. alveolar bone during the development and throughout adulthood [1C4]. FGF signaling occupies a significant position in inducing the proliferation and differentiation of multiple cell types during embryonic stages [5C10], as well as in regulating the development in different animals [11C14]. In addition, FGFs have been shown to regulate mouse tooth development [2, 15C17]. Nevertheless, a comprehensive description about the mechanism underlying FGFs that regulate different mineralized tissues of tooth during the embryonic stages, as well as incisor renewal in the adulthood, is still needed. Here, we summarize the roles of FGF signaling in mouse tooth development and the ways FGFs control the stem cells in incisor renewal, trying to separate its different functions and highlighting the crosstalk between FGFs and other signaling pathways. 2. Development of Tooth and Supporting Bone Structure Most vertebrate groups have the ability to replace their teeth. Mammals have two sets of teeth: main and adult teeth. In contrast, mice contain one arranged with two different types: molars located in the proximal area and incisor located in the distal area, which are separated from the toothless diastema region. Mouse incisors grow continuously throughout the lifetime in razor-sharp contrast to the molars. It has been 4-Chloro-DL-phenylalanine shown that the presence of stem cells, which are located in the proximal end of the incisor, gives rise to the differentiated tooth cell types, therefore promoting continuous growth of this tooth [18]. It has been widely held that tooth morphogenesis is characterized by the sequential relationships between the mesenchymal cells derived from the cranial neural crest, and the stomadial epithelium [19, 20]. This process consists of several 4-Chloro-DL-phenylalanine phases, that is, bud, cap, and bell phases. In mice, the dental care mesenchyme is attributed to neural crest cells which are derived from the midbrain and hindbrain areas around embryonic day time 8.5 (E8.5) [21C24]. The dedication of tooth-forming sites during E10.5 [25C27] and the thickening of the dental care epithelium at E11.5 have been considered as the first signs of tooth development [28]. During the bud stage (E12.5CE13.5), in both incisor and molar, the thickened dental care epithelium buds into the underlying mesenchyme, thus forming the epithelial tooth bud round the condensed mesenchymal cells. At the subsequent cap stage (E14.5CE15.5), the epithelial component undergoes specific folding. A central event, during the transitional process between bud and cap phases, is the formation of the enamel knot (EK), a structure composed of a group of nondividing cells. Moreover, several signaling molecules, such as Shh, FGF4, FGF9, BMP4, and BMP7, as well as Wnt10a/b, are restrictedly indicated in the enamel knot. Several studies have shown the EK, as the signaling center, has an important role in tooth cusp patterning control [29, 30]. During the following bell stage, the ameloblasts and odontoblasts originate from the dental care epithelium and mesenchyme, respectively [2]. At this stage, the secondary EKs (sEK) succeed the primary EKs (pEK) in the molar. In addition, the condensed mesenchymal cells round the developing epithelial tooth germ in the bud stage go on to differentiate into a assisting alveolar bone that forms the sockets for the teeth in the bell stage [31C33]. With reference to its origin, it has been reported the alveolar bone is definitely created by intramembranous ossification [32, 33]. Intramembranous ossification starts with the mesenchymal cells which are derived from embryonic lineages correspondingly, which then migrate towards locations of the future bones. Here, they form high cellular denseness.This is consistent with the mutants develop a severely hypoplastic LaCL and either thin or missing enamel layer, suggesting that FGF signaling levels have an important role in the maintenance of the epithelial stem cell pool in the incisor [80]. and alveolar bone during the development and throughout adulthood [1C4]. FGF signaling occupies a significant position in inducing the proliferation and differentiation of multiple cell types during embryonic phases [5C10], as well as with regulating the development in different animals [11C14]. In addition, FGFs have been shown to regulate mouse tooth development [2, 15C17]. However, a comprehensive description about the mechanism underlying FGFs that regulate different mineralized cells of tooth during the embryonic phases, as well as incisor renewal in the adulthood, is still needed. Here, we summarize the functions of FGF signaling in mouse tooth development and the ways FGFs control the stem cells in incisor renewal, trying to separate its different functions and highlighting the crosstalk between FGFs and additional signaling pathways. 2. Development of Tooth and Supporting Bone Structure Most vertebrate groups have the ability to replace their teeth. Mammals have two units of teeth: main and adult teeth. In contrast, mice contain one arranged with two different types: molars located in the proximal area and incisor located in the distal area, which are separated from the toothless diastema region. Mouse incisors grow continuously throughout the lifetime in razor-sharp contrast to the molars. It has been shown that the presence of stem cells, which are located in the proximal end of the incisor, gives rise to the differentiated tooth cell types, therefore promoting continuous growth of this tooth [18]. It has been widely held that tooth morphogenesis is characterized by the sequential relationships between the mesenchymal cells derived from the cranial neural crest, and the stomadial epithelium [19, 20]. This process consists of several phases, that is, bud, cap, and bell phases. In mice, the dental care mesenchyme is attributed to neural crest cells which are derived from the midbrain and hindbrain areas around embryonic day time 8.5 (E8.5) [21C24]. The dedication of tooth-forming sites during E10.5 [25C27] and the thickening of the dental care epithelium at E11.5 have been considered as the first signs of tooth development [28]. During the bud stage (E12.5CE13.5), in both incisor and molar, the thickened dental care epithelium buds into the underlying mesenchyme, thus forming the epithelial tooth bud round the condensed mesenchymal cells. At the subsequent cap stage (E14.5CE15.5), the epithelial component undergoes specific folding. A central event, during the transitional process between bud and cap phases, is the formation of the enamel knot (EK), a structure composed of a group of nondividing cells. Moreover, several signaling molecules, such as Shh, FGF4, FGF9, BMP4, and BMP7, Hsp25 as well as Wnt10a/b, are restrictedly indicated in the enamel knot. Several studies have shown the EK, as the signaling center, has an important role in tooth cusp patterning control [29, 30]. During the following bell stage, the ameloblasts and odontoblasts originate from the dental care epithelium and mesenchyme, respectively [2]. At this stage, the secondary EKs (sEK) succeed the primary EKs (pEK) in the molar. In addition, the condensed mesenchymal cells round the developing epithelial tooth germ in the bud stage go on to differentiate into a assisting alveolar bone that forms the sockets for the teeth in the bell stage [31C33]. With reference to its origin, it has been reported the alveolar bone is definitely created by intramembranous ossification [32, 33]. Intramembranous ossification starts with the mesenchymal cells which are derived from embryonic lineages correspondingly, which then migrate towards locations of the future bones. Here, they form high cellular denseness.