The adrenal cortex continuously remodels in response to physiological cues, though the precise cellular and molecular mechanisms remain poorly understood. Our prior studies show that the adrenal cortex undergoes zonal transdifferentiation during postnatal development in the zona Glomerulosa (zG) gives rise to the zona Fasciculata (zF). This process involves formation and resolution of multicellular zG-rosettes via the adherens junction(AJ)-aCatenin complex. How these structures regulate aldosterone production and how dysregulation leads to disease is not known. Given that primary aldosteronism (PA), the most common form of endocrine hypertension, involves hyperplasic expansion of zG-rosettes, further study of the factors and signaling pathways involved in regulating zG development and maintenance is warranted. Utilizing a zG-specific b-catenin gain-of- function mouse model, we have shown that zG hyperplasia in PA is driven by a block in rosette resolution/transdifferentiation. In addition, this block involves up regulation of FGFR2 signaling, which is required for rosette formation during normal development. Further, we have found that rosettes act as a coordinating center for Ca2+ signaling, via the AJ-aCatenin complex, and subsequent aldosterone production. We also discovered that WNT2B, recently identified by GWAS analysis as a major risk allele for PA, is a novel regulator of aldosterone production and zG homeostasis. Based on our recent findings, it is increasing evident that further study of the role of AJs, rosettes and the signals that control them is necessary. Thus, we propose the following: Aim 1. Define how WNT2B mediates zG morphogenesis and function. Aim 2. Determine how a-Catenin and AJs mediate zG morphogenesis and function. Aim 3. Establish how FGFR2 regulates zG morphogenesis and function. These studies seek to understand the regulatory mechanisms that control zG function during postnatal development and maintenance. The successful completion of these studies will provide critical insights into the mechanisms that govern zG homeostasis and the initiation and progression of PA, which may lead to new targeted therapies for this disease.