Fig. 5

Illustration of the dynamics of Nodal distribution and availability during differentiation of GBM stem cells and of the endocytic mechanisms that may regulate Nodal during GBM tumorigenesis. The GBM stem cells shows a large amount of Nodal symmetrically distributed in their cytoplasm. The presence of Nodal in these cells is co-localization with both early (EEA1 and Rab5) and late (Rab7 and Rab11) endosomes. Upon differentiation, an asymmetric distribution of Nodal is found in the perinuclear region of the cells. In these cells, the intra and extracellular levels of Nodal are reduced and its co-localization with endosomes changes. There is a decrease in the association of Nodal with early (EEA1 and Rab5) endosomes and increase in its association with late (Rab7 and Rab11) endosomes. The characteristics seen in the stem cells can be returned after the dedifferentiation of the cells