Amelogenesis is a complicated process as described

Amelogenesis is a complicated process, as described above, and for the last several decades, various animal and human studies have used molecular genetics to identify a number of signaling molecules and gene networks that act at specific stages of the ameloblast life cycle and regulate its patterning and differentiation processes. Rho GTPases, including RhoA, Rac1, and Cdc42, have been identified as the regulatory mechanism for cellular events such as migration, polarization, cytokinesis, cell–cell adhesion, cell cycle, and gene expression in many cell types [8], [9], [10]. Until recently, Rho GTPases were believed to be involved primarily in the regulation of cytoskeletal organization in response to extracellular molecules. However, recent studies have demonstrated that they play crucial roles in many cellular events such as transcriptional activation, cell proliferation, cell polarity, cell–cell adhesion, membrane trafficking, muscle contraction, ion channel activity, endothelial permeability, reactive oxygen species production, phospholipid metabolism, and embryonic development [9], [11]. Further, they are involved in osteoclastogenesis as well as in hematopoiesis and hemopathies [12], [13]. Recently, evidence has emerged showing the involvement of Rho signaling in tooth development [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24]. In this article, we summarize some interesting recent findings that provide molecular insights into how signaling by Rho GTPases results in tooth development, focusing on ameloblast differentiation in particular.
General aspects of Rho GTPases
Implication of Rho GTPases signaling in ameloblasts
Rho GTPases in ameloblastomas Interestingly, it appears that Rho GTPase plays a crucial role not only in normal ameloblasts differentiation but also in pathologies such as ameloblastomas. A study using immunohistochemistry to analyze the expression and distribution of Rho GTPase in solid and unicystic amemoblastomas reported that RhoA and Rho B were observed in a high number of A922500 and also had greater intensity in nonpolarized cells in all follicular, plexiform, and unicystic ameloblastomas. Comparison of differences in solid and unicystic variations was significant with the unicystic variant showing a higher number of positive cells [87]. Similarly, Cdc42 expresses stronger in nonpolarized cells than in basal polarized cells in all types of ameloblastomas. The unicystic subtype showed a higher number of positive cells compared with the solid ameloblastomas [87]. These results suggest that Rho GTPase plays a role in the determination of epithetical cell phenotypes, variants, and subtypes in ameloblastomas.
Concluding remarks
Conflicts of interest
Introduction During brain development, each neuron typically outgrowths several neurites, which then develop into a single axon and multiple dendrites and eventually form synapses (Elston and Fujita, 2014, Goldberg, 2003, Kolodkin and Tessier-Lavigne, 2011, McAllister, 2007). To ensure precise neuronal connectivity, neurons evolve spatial and temporal coordination of multiple developmental steps, including axon specification (Cheng and Poo, 2012, Tahirovic and Bradke, 2009, Takano et al., 2015, Villarroel-Campos et al., 2016), axon outgrowth and branching (Kalil and Dent 2014), axon retraction/pruning (Luo and O'Leary, 2005, Riccomagno and Kolodkin, 2015), axon guidance and navigation (Chedotal and Richards, 2010, O'Donnell et al., 2009, Quinn and Wadsworth, 2008, Raper and Mason, 2010), the selection of synaptic target sites, dendritic growth and branching, and synapse formation and maturation (de la Torre-Ubieta and Bonni, 2011, Elston and Fujita, 2014, Kolodkin and Tessier-Lavigne, 2011, McAllister, 2007, Williams et al., 2010). The impairment of these steps have profound effects on brain function and are linked to developmental disorders of the central nervous system (CNS), which range from intellectual disability to epilepsy, autism, and schizophrenia (Clement et al., 2012, Pavlowsky et al., 2012, Ramakers, 2002, Schubert et al., 2015, Stankiewicz and Linseman, 2014). To understand how the precise refinement and coordination are carried out, it is crucial to decode the role of key proteins in this process.