Figure 7. Model for planarian epidermal differentiation.

(A) Top panel: Planarian epidermal cells mature in a spatiotemporally defined sequence, in which progenitors go through several transitions defined by cellular morphology and spatial distribution. Bottom panel: Genes that are associated with distinct epidermal identities are expressed in all stages of the epidermal maturation, in a spatially-defined manner. Some of these genes are already expressed in ζneoblasts suggesting that ζneoblasts sense their position in the animal. (B) Some spatially-restricted epidermal identities are pre-patterned in epidermal progenitors. The model presents a view of a transverse cross-section. Dorsal is up. Medial mature epidermal cells (M; Large shapes) express ovo-2 (yellow nuclei), whereas lateral cells do not (L; purple nuclei). FISH analysis of epidermal progenitors determined that epidermal progenitors near the midline already express ovo-2 (yellow), whereas lateral epidermal progenitors do not (purple). (C) The specification of ζneoblasts to ventral (kal1+) identities is repressed by bmp4 expression from dorsal muscle cells (red elongated cells). ζneoblasts, which are in proximity to the BMP source, can express dorsal markers (PRDM1-1+; green circles), which is correlated with the emergence of additional dorsal epidermal identities. By contrast, cells that are far from the BMP source can specialize to ventral progenitors (kal1+; blue circles), which are associated with ventral epidermal identities. Inhibition of BMP signaling results in the emergence of kal1+ ζneoblasts dorsally. (D) BMP inhibits the expression of genes associated with a ventral identity in dorsal ζneoblasts. Inhibition of BMP leads to emergence of ventral identities dorsally.