The two-step CNS developmental landscape.

<p>To map the two-step landscape for CNS differentiation, we first calculated the bifurcation diagram of fate-switch genes using the gene expression of to represent the development process. Based on this bifurcation diagram, we identified the parameter region for the first and the second step development. Then we calculated and glued the first-step and the second-step landscape in an <i>ad hoc</i> coordinate system to obtain the two-step developmental landscape, which is similar to the original Waddington’s landscape. (a) The bifurcation diagram for two fate-switch genes motifs under the change of . Here we only showed the stable fixed point. Line I indicates the boundary for the first-step differentiation, which is used in constructing subfigure b (the first-step landscape). Line II indicates the boundary for the second-step differentiation, which is used in constructing subfigure c. The cut-off values of 2.0 and 0.9 at the line I and line II are the values where the bifurcation reaches the largest region and that the corresponding differentiation step is assumed to be completed. (b) The first-step landscape for - motif which describes the CNS precursors develops into neurons and glia. The left neuron valley of the landscape will be extended during the construction of CNS development landscape. (c) The second-step landscape for - motif which describes glia develops into astrocyte and oligodendrocyte. The mesh size in mapping this landscape can be adjusted to align the joining attractors from first and second-step landscapes. This landscape was further compressed and its left and right boundaries were cut off during following construction of the CNS development landscape. (d) The two-step CNS developmental landscape. This landscape is constructed by gluing the first and the second step development landscape and the extending landscape, respectively symbolized as region A, region B and region C. Three specific steps were involved during the gluing of the CNS development landscape. The dominant paths are also shown on the landscape. Yellow color lines represent the development processes while red color lines represent the retrodifferentiation processes. The transdifferentiation paths need firstly move back to the CNS progenitors and then downward to the target cell types (Data not shown). Thus the transdifferentiation paths can be regarded as a combination of retrodifferentiation and dedifferentaition processes.