Figure 7. Alternative hypotheses proposed for stem cell maintenance of the adrenal cortex.

Each hypothesis is modified to include putative stem cells (blue stars) that produce TACs which divide, the offspring of which move in the direction of the vertical arrows, gradually differentiating and eventually dying near the arrowheads. (A) Classical centripetal migration hypothesis: a single stem cell population in the outer cortex gives rise to new TACs that displace existing cells inwards, transdifferentiating from ZG to ZF to ZR to maintain all three zones (reviewed in 37); (B) Variant centripetal migration hypothesis: similar to (A), except that stem cells are located in the adrenal capsule (reviewed in 1); (C) “Intermediate field” hypothesis: variant of (A) in which stem cells located at the tips of looped strings of cells close to the ZG/ZI boundary, give rise to TACs that move along the strings, first outwards towards the capsule and then arc around to move inwards, following a trajectory shaped like a ‘walking stick’ (reviewed in 37); (D) Zonal hypothesis: each cortical zone is maintained independently by resident stem cells (reviewed in 37); (E) Independent inward migration in three zones: variant of (D) with inward cell movement; (F) Independent inward migration in two zones: variant of (E) where ZF and ZR are maintained by a single stem cell population; (G,H) ZI stem cells: where either two separate stem cell populations or a single bipotential stem cell population in the ZI maintain both the ZG and ZF/ZR [2]; (I) Two separate lineages from outer stem cells: variant hypothesis proposing that stem cells in the outer cortex or capsule produce TACs, which either differentiate into ZG cells or move inwards to become ZF/ZR cells. The ZG and ZF/ZR lineages may be produced either by a single bipotential population or two separate populations of stem/progenitor cells. Unlike (A-C), differentiated steroidogenic ZG cells do not transdifferentiate into ZF/ZR cells.