Fig. 10. Model of NLK function during germ layer specification and position of NLK in the endomesoderm gene regulatory network. (A) Model of NLK function during segregation of the mesoderm. Treatment with lithium increases the size of the endodermal territory and shifts the ectoderm/endoderm boundary towards the animal pole. Overerexpression of NLK or Delta causes the mesodermal territory to expand and the endodermal/ectodermal boundary to be displaced towards the animal pole. Co-injection of NLK and Delta converts most cells of the embryo into mesoderm. (B) Role of NLK in the gene regulatory network regulating mesoderm formation. During cleavage stages, the maternal Wnt pathway acting through TCF induces the endomesoderm. At the blastula stage, Notch/Delta signalling upregulates the expression of nlk in mesodermal precursors. NLK promotes segregation of the mesoderm from the endomesoderm by downregulating TCF in the presumptive SMCs, allowing the establishment of a novel regulatory domain that expresses mesodermal genes such as gcm. NLK and Delta maintain the expression of each other. The NLK and ERK pathways converge to maintain specification of SMCs, while NLK, possibly acting upstream of the MAP kinase pathway, promotes epithelial mesenchymal transition by stimulating phosphorylation of ERK and expression of ets1.