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

Sining Leng, Emanuele Pignatti, Radhika S. Khetani, Manasvi S. Shah, Simiao Xu, Ji Miao, Makoto M. Taketo, Felix Beuschlein, Paula Q. Barrett, Diana L. Carlone and David T. Breault ()
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Sining Leng: Boston Children’s Hospital
Emanuele Pignatti: Boston Children’s Hospital
Radhika S. Khetani: Harvard T.H. Chan School of Public Health
Manasvi S. Shah: Boston Children’s Hospital
Simiao Xu: Boston Children’s Hospital
Ji Miao: Boston Children’s Hospital
Makoto M. Taketo: Kyoto University
Felix Beuschlein: UniversitätsSpital Zürich
Paula Q. Barrett: University of Virginia
Diana L. Carlone: Boston Children’s Hospital
David T. Breault: Boston Children’s Hospital

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-15332-7

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