Figure 8. A model for the role of PTEN in the formation of the pseudostratified columnar epithelium.
PDPK1 is anchored to the plasma membrane by PtdIns(3,4,5)P3 (PIP3), which is made by PI3 kinase (PI3K) and degraded by PTEN. In the Pten mutant, increased PIP3 recruits high levels of PDPK1 to the membrane, where it is activated. Activated membrane-associated PDPK1 has two targets: activated PDPK1 generates high levels of pAKT; in a separate pathway, high levels of membrane-associated PDPK1 inhibit the formation of stable apical junctions. Stable apical junctions are required for the formation of stable apical-basal microtubule arrays, which mediate apical-to-basal trafficking in the neural epithelium, allowing elongation and tight packing of cells in the neural epithelium. In WT, PDPK1 is not required for formation of the pseudostratified neural epithelium, although the delay in neural tube closure in Pdpk1 mutants may reflect a subtle role for the protein in epithelial organization.