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. 2010 May 19;5(5):e10706. doi: 10.1371/journal.pone.0010706

Figure 7. Induction of Mixl1 expression is regulated through the integration of signals from BMP, Wnt and Activin/nodal pathways.

Figure 7

(A) Interactions between signalling pathways and inhibitors impacting upon Mixl1 induction. BMP4 stimulates expression of Wnt and Activin/nodal, which in turn induce Mixl1, perhaps acting through as yet unidentified intermediate molecules. The time periods (in days) and differentiation stages during which the differentiating ES cells are responsive to each stimulus are indicated. Probable autocrine (A) and paracrine (P) roles of the factors are indicated. (B) Removal of factors maintaining pluripotency enables ES cells to differentiate and to respond to BMP4, Wnt3a or Activin A signals delivered during a defined ‘temporal window’ for mesendoderm induction. (C) After cells pass through the mesendoderm window at d3, they then pass through ‘exit gates’ for each signalling pathway, after which time they are no longer dependent on that pathway for mesendoderm induction. In response to BMP4 addition between d1.5 and d3, the approximate percentage of cells that have passed the BMP4, Wnt3a or Activin A ‘exit gates’ at d3 is shown. See text for more details (Data taken from Figure 5B).