\u03b2-Catenin and FGFR2 regulate postnatal rosette-based adrenocortical morphogenesis

Sining Leng,Manasvi S Shah,Diana L Carlone,Felix Beuschlein,Emanuele Pignatti,Makoto M Taketo,Simiao Xu,Ji Miao,Paula Q Barrett,Radhika S Khetani,David T Breault

doi:10.1038/s41467-020-15332-7

Abstract

Rosettes are widely used in epithelial morphogenesis during embryonic development and organogenesis. However, their role in postnatal development and adult tissue maintenance remains largely unknown. Here, we show zona glomerulosa cells in the adult adrenal cortex organize into rosettes through adherens junction-mediated constriction, and that rosette formation underlies the maturation of adrenal glomerular structure postnatally. Using genetic mouse models, we show loss of β-catenin results in disrupted adherens junctions, reduced rosette number, and dysmorphic glomeruli, whereas β-catenin stabilization leads to increased adherens junction abundance, more rosettes, and glomerular expansion. Furthermore, we uncover numerous known regulators of epithelial morphogenesis enriched in β-catenin-stabilized adrenals. Among these genes, we show Fgfr2 is required for adrenal rosette formation by regulating adherens junction abundance and aggregation. Together, our data provide an example of rosette-mediated postnatal tissue morphogenesis and a framework for studying the role of rosettes in adult zona glomerulosa tissue maintenance and function.

Highlights

Rosettes are widely used in epithelial morphogenesis during embryonic development and organogenesis
We co-stained for the Gq alpha subunit (Gαq), a marker of mature zona glomerulosa (zG) cells, and classic basement membrane (BM) components such as laminin and type IV collagen
From a 2D cross-sectional viewpoint, glomeruli are distinct clusters of zG cells surrounded by a laminin subunit β1 (Lamb1)-rich BM (Fig. 1a)

Summary

Introduction

Rosettes are widely used in epithelial morphogenesis during embryonic development and organogenesis. We show zona glomerulosa cells in the adult adrenal cortex organize into rosettes through adherens junction-mediated constriction, and that rosette formation underlies the maturation of adrenal glomerular structure postnatally. The exact nature of these structures and their functional significance in the adult adrenal has never been investigated Given their role in mediating tissue morphogenesis, one appealing hypothesis is that rosette formation and resolution underlie the establishment and remodeling of zone-specific tissue morphology. These questions cannot be addressed without a detailed understanding of the adrenal glomerulus structure and the mechanisms governing its formation. Using confocal imaging and 3D reconstruction, we show that glomeruli in the adult zG are interconnected globular structures enwrapped in a Laminin β1-

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Conclusion