Figure 2.

Crosstalk between the three distinct oscillators that function in the mouse PSM.

(a) Schematic diagram of a signalling and a responding cell in the mouse PSM, detailing cyclic genes of the Notch, Fgf and Wnt pathways. Notch and Fgf-regulated cyclic genes oscillate asynchronously to cyclic genes of the Wnt pathway [56]. A large number of the cyclic genes are involved in negative feedback loops [3]. The very basic circuitry of the three signalling pathways is represented here. N.B. Hes7 expression is Fgf-dependent in the caudal PSM only. Hashed line represents interactions that to date have only been shown in tissues outside of the PSM [75,78]. (b) The crosstalk indicated between the three pathways in this part of the figure are interactions that have been demonstrated specifically within the PSM largely through the analysis of mouse mutants and some pharmacological studies [33,53,54,56,58–60,70,79]. As such, it is not clear if these interactions are direct. These analyses rely on analysis of mRNA expression of the various pathway components as indicated by italicised gene names. The interactions are colour coded such that regulation of the Wnt or Fgf pathway components by the Notch pathway are indicated in pink, input from the Wnt signalling pathway to the regulation of Notch or Fgf components are in blue. Regulation of the Notch or Wnt pathway components by the Fgf pathway is indicated in green. Dll1, Delta-like 1; DACT1, dapper homologue 1; DSH, dishevelled; DUSP4/6, dual specificity phosphatase 4/6; FGFR1, FGF receptor 1; GSK3, glycogen synthase kinase 3; Hes7, hairy and enhancer of split related 7; LFNG, lunatic fringe; LRP, low density lipoprotein receptor-related protein; NICD, Notch intracellular domain; NKD1, naked cuticle 1 homologue; Nrarp, Notch-regulated ankyrin repeat protein; RBP, recombination signal binding protein for immunoglobulin kappa J region; Spry 2/4, sprouty 2 and sprouty 4; CKI, Casein kinase I. ERK, mitogen-activated protein kinase 1 (MAPKK); MEK, mitogen-activated protein (MAPK); Raf, MAP kinase kinase kinase (MAP3K); Ras, small GTPase; GRB2, growth factor receptor-bound protein 2; SHP2, Src homology region 2-containing protein tyrosine phosphatase 2; SOS, son of sevenless; FRS2, Fibroblast growth factor receptor substrate 2; APC, protein encoded by the adenomatosis polyposis coli gene; Lef, Lymphoid enhancer-binding factor; Hey, Hairy/enhancer-of-split related with YRPW motif protein; TF, Transcription factor complex.