TOWARDS AN INTEGRATED VIEW OF Wnt SIGNALING IN MOUSE ADRENOCORTICAL FUNCTIONAL ZONATION

The adrenal gland is composed of two ontogenetically and functionally distinct t issues, the medulla and the cortex. The cortex, the subject of the present art icle, forms the major part of the murine gland and is further organized into three concentric layers: the outer zona glomerulosa, the zona fasciculata and the innermost X-zone. Specific hormonal production is finely tuned in t ime and space, in relation with the structure and functional organization of the adrenal cortex. This t ight, reciprocal regulation of adrenocortical steroid-synthesizing enzymes is termed functional zonat ion. Maintenance of adrenal gland structure and function is regulated through the integration of extraand intracellular signals that have only recently started to be defined. To study specif ically the role of Wnt signaling pathway in normal adrenocortical funct ional zonation, the TWIK-related acidsensit ive potassium channel 1 (Task1) knockout mice are likely to become a valuable tool as it is the first model for severe but reversible disorganization of the adrenal cortex. In the realtime polymerase chain reaction (RT-PCR) experiments, the relative mRNA expression levels of Wnt4, the two antagonists Dkk3 and Sfrp4 and the membrane receptor Ror2 in the adrenals of young (postnatal day 15) and adult (postnatal day 40) Task1 null mice of both sexes coordinately with the phenotype versus their corresponding wild-type mice were analyzed. It has been shown, in this study, that only Dkk3 expression is signif icantly upregulated in adult female Task1 /mice. This f inding reveals that Dkk3 plays a role in adrenocortical functional zonation and further reinforce the evidence suggesting a key role for the Wnt signaling pathway in regulating the production of aldosterone in the adrenal cortex.