ORIGINS OF ZONATION - THE ADRENOCORTICAL MODEL OF TISSUE-DEVELOPMENT AND DIFFERENTIATION

1. Although much work has addressed the functional significance of mam malian adrenocortical zonation,less attention has been paid to its dev elopmental origins and the factors that maintain it. Recent concepts o f tissue differentiation hold that cells respond to local morphogenic stimuli that are generated in a paracrine manner. 2. In fact, the adre nal cortex represents an ideal mammalian in vivo model for such studie s: few others exist. While several components may contribute to the es tablishment of a developmental polarity in the gland, including produc ts of capsular and neural elements, compelling evidence now suggests t hat the tissue renin-angiotensin system (RAS) has a critical role. 3. We have examined the roles of these and other paracrine morphogens and growth factors and of specific transcription factors in adrenocortica l cellular proliferation and development. From data obtained by using in situ hybridization to determine their cellular location, we propose a hierarchy of potential tissue modelling agents. These include morph ogens, such as angiotensin II derived from the intra-adrenal RAS, grow th factors (e.g. basic fibroblast growth factor), which can be conside red to be the paracrine amplifiers of the morphogenic signal, and, fin ally; transcription factors, such as C-fos, that directly stimulate mi tosis and other events of differentiation.