β-Catenin and FGFR2 regulate postnatal rosette-based adrenocortical morphogenesis

• Published in: Nature communications 2020-04, Vol.11 (1), p.1680-1680, Article 1680
• Main Authors: Leng, Sining, Pignatti, Emanuele, Khetani, Radhika S., Shah, Manasvi S., Xu, Simiao, Miao, Ji, Taketo, Makoto M., Beuschlein, Felix, Barrett, Paula Q., Carlone, Diana L., Breault, David T.
• Format: Article
• Language: English
• Subjects: 13/1; 13/51; 14; 14/19; 14/28; 38/77; 38/88; 38/90; 38/91; 631/136/1660/1986; 631/80/79/2028; 64/60; Adherens junctions; Adherens Junctions - genetics; Adherens Junctions - metabolism; Adherens Junctions - ultrastructure; Adrenal cortex; Adrenal Gland Neoplasms - surgery; Adrenal glands; Animal models; Animals; Animals, Newborn; beta Catenin - genetics; beta Catenin - metabolism; Embryogenesis; Embryonic growth stage; Female; Fibroblast growth factor receptor 2; Humanities and Social Sciences; Humans; Maintenance; Male; Mice; Mice, Knockout; Microscopy, Electron, Transmission; Morphogenesis; multidisciplinary; Organogenesis; Receptor, Fibroblast Growth Factor, Type 2 - genetics; Receptor, Fibroblast Growth Factor, Type 2 - metabolism; Regulators; Rosette formation; Science; Science (multidisciplinary); Tissues; Zona Glomerulosa - cytology; Zona Glomerulosa - growth & development; Zona Glomerulosa - metabolism; Zona Glomerulosa - ultrastructure; β-Catenin
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-15332-7

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. Multicellular rosettes are known to mediate complex cellular reorganization such as epithelial folding and branching during embryonal organogenesis. Here the authors show that rosette formation regulated by β-Catenin and FGFR2 mediate postnatal adrenal cortex zona glomerulosa morphogenesis.