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FIG. 5. Barhl2 acts as a brake on diencephalic progenitor proliferation. (a) barhl2, wnt, and shh ligands are coexpressed in the diencephalic
primordium. The scheme of a stage 27 neural tube: barhl2 (yellow) is expressed in the prosomere p2 (p2) within the diencephalon, in a territory
giving rise to the ZLI, a secondary organizer that secretes Shh (blue). Shh is also expressed in the anterior neural tube basal plate. Wnt3a (in
red) as Wnt3 (data not shown) is expressed in the dorsal (alar plate) part of the prosomere p2, in the midbrain roof plate. The two other major
secondary organizers, the ANR (pink) and the isthmic organizer (isO, green), that play roles in patterning the forebrain and the midbrain/hindbrain,
respectively, are also shown. The secretion is represented with arrows. Whole mount ISH using barhl2, shh, or wnt3a probes as indicated.
Representative dissected neural tube of wild-type embryos is shown, dorsal view anterior left. Whole mount TUNEL analysis: cells
undergoing endogenous apoptosis appear in blue. (b) Nonapoptotic functions of caspases regulate the levels and activity of b-catenin. In Xenopus
diencephalic primordium, Barhl2 acts upstream of a nonapoptotic function of caspase-3 that limits both levels and activity of b-catenin
and consequently limits the proliferation of neural progenitors, controls the neuroepithelium architecture, and regulates the transcription of
Wnt target genes. In drosophila SOP cells, the caspases orthologues DRONC and drICE limit the activity of the Wingless pathway by cleaving
an isoform of GSK3-b, Shaggy, which destabilizes Armadillo (b-catenin orthologue) and consequently limits the Wnt pathway. |