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Figure 7


Fig. 7. Summary schematic of distinct subdivisions in the hindbrain roof plate, their differential contribution to the hindbrain choroid plexus and differential responses among rhombic lip lineages to activated Notch1. Wnt1 mRNA in the rhombic lip is graded, with the highest expressers giving rise to hindbrain roof plate epithelium (hRPe) beginning at ~E8. These cells emerge from the rhombic lip and occupy the entire hRPe by ~E9.5 (yellow); they intermix in the anteroposterior (AP) and dorsoventral (DV) dimensions and are highly proliferative. Beginning at ~E9.25-E9.5, Gdf7 expression starts in the dorsal-most progenitor cells in the rhombic lip and these progenitors give rise to hRPe (dark blue) that is compartmentalized in both the AP and DV dimensions, settles laterally and is non-mitotic immediately upon emerging from the rhombic lip. The medially located (yellow) hRPe cells have a history of Wnt1 expression, whereas the laterally located (dark blue) hRPe cells have a history of both Wnt1 and Gdf7 expression. Caudally (r2-r8)-derived lateral hRPe (light blue) expresses Ttr and Kcne2 from ~E9.5 onwards, whereas expression in rostrally (r1)-derived cells only occurs after E12.5. Beginning at ~E12.5, laterally located hRPe cells (light and dark blue) undergo cell shape changes to form the hindbrain choroid plexus epithelium (hCPe) (not drawn to scale). Medially located hRPe cells (yellow) do not appear to contribute to the hCPe. From ~E12.5 through to E14, Gdf7+ progenitors within the rhombic lip probably generate hCPe cells directly, without seeming to transition through an hRPe intermediate. At ~E14, the production interval for hCPe ceases. Ligand-independent activation of the Notch1 signaling pathway in the Gdf7 lineage (the hRPe and hCPe lineage) results in overproliferation of hCPe. 4v, fourth ventricle; hCP, hindbrain choroid plexus; mes, mesenchymal cells.