The organization of the axial skeleton and skeletal muscles is bilaterally symmetric. In contrast, vertebrates are also character- ized by stereotypic LR asymmetries in the distribution of the internal organs such as the heart and stomach on the left, and the liver on the right. The axial skeleton and skeletal muscles are derived from embryonic structures called the somites. The epithelialization of a new pair of somites occurs in a bilateral symmetric manner from the anterior-most region of the mesenchymal presomitic meso- derm. This process is tightly regulated in space and time, with a new pair of somites of approximately the same size being formed with a regular species-specific time period. The ‘‘clock and wavefront’’ model postulates the existence of two independent phenomena accounting for periodic somite formation. The clock is evident in the PSM as periodic oscillations in gene expression of the so-called cyclic genes. These genes show a dynamic and reiterated expression in PSM cells with the same periodicity of somite formation. Although the list of cycling genes is increasing, the conserved ones across species include mainly Notch targets, namely the bHLH transcription repressors, the hes genes in the mouse and the her genes in zebrafish. More recently, a large scale transcriptome analysis revealed that the segmentation clock mechanism shows different degrees of complexity between mouse and zebrafish. In the mouse, Trihexyphenidyl HCl many of the cyclic genes belong not only to the Notch pathway but also to the Wnt and FGF pathways. In zebrafish there is no evidence for the existence of cyclic genes of the Wnt or FGF pathways. In addition to the presence of a molecular clock, the PSM cells are under the influence of a wavefront of differentitaion. This wavefront is determined by gradients of Fgf and Wnt signalling coming from the posterior region of the embryo and fading towards the anterior portion of the PSM. While under the influence of Fgf/Wnt signalling, the PSM cells are maintained in an immature state and are prevented from starting the genetic program of somite formation. Soon after being formed the somites differentiate into the dermomyotome, which segregates into the dermal layer of the skin and skeletal muscles, Tolclofos-methyl and into the sclerotome that forms the vertebral column. At the same time somites are being formed, left-right asymmetric information is establishing laterality in the nearby lateral plate mesoderm, culminating with the asymmetric positioning of internal organs. Before there are any signs of asymmetric organ localization in the vertebrate embryo, a conserved cascade of asymmetrically expressed genes is activated around the node in the mouse and around the Kupffer’s vesicle, the functionally equivalent fish organ. An excess of Nodal activity on the left side of the node/KV is transferred to the left LPM and in this location Nodal exerts a positive feedback on itself. As a consequence, the expression of nodal is amplified in the left LPM. Nodal also activates its negative regulators, the lefty genes. Lefty1 in the midline prevents nodal activation on the right LPM, while Lefty2 restricts the domain of nodal expression on the left LPM. The strong nodal expression on the left LPM induces pitx2 expression that in turn activates morphogenetic proteins required for LR asymmetry of the internal organs. Even though this Nodal cascade is conserved, the mechanism that induces nodal in the node/KV is different between vertebrates. Notch signaling activates nodal in the murine node region, while in zebrafish it activates the Nodal negative regulator charon around the KV.