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.