Sonic hedgehog signaling during adrenal development

It has been speculated for a number of years that Sonic hedgehog (Shh) signaling plays an important role in adrenal development. Over the past two years several reports have described the expression and function of Shh pathway genes in the adrenal cortex, using primarily mouse models. The key findings are that Shh signals produced by a population of partially differentiated cortical cells located in the outer cortex/zona glomerulosa are received by non-cortical mesenchymal cells located predominantly in the overlying capsule. This signal is required for growth of both the capsule and the cortex, but not for cortical zonation or steroidogenic cell differentiation. Using molecular genetic tools to define the adrenocortical cell lineages that are descended from both Shh signaling and receiving cells, both capsule and cortical cells were found to have properties of adrenocortical stem and/or progenitor cells. Here we place these observations within the context of prior studies on adrenal development, postnatal adrenal maintenance and adrenocortical stem/progenitor cell lineages.

► Shh signal produced by partially differentiated outer cortical/zona glomerulosa cells.
► Signal received only by non-cortical mesenchyme cells, predominantly in capsule.
► Capsule and cortex growth need Shh; zonation and steroidogenic differentiation do not.
► Pallister–Hall syndrome mice (Gli3Δ699/Δ699) have adrenal glands.
► Lineage analyses show Shh and Gli1 expression mark cortical stem/progenitor cells.