β-Catenin and FGFR2 regulate postnatal rosette-based adrenocortical morphogenesis.
Sining Leng,Sining Leng,Emanuele Pignatti,Emanuele Pignatti,Radhika S. Khetani,Manasvi S. Shah,Manasvi S. Shah,Simiao Xu,Simiao Xu,Ji Miao,Ji Miao,Makoto Mark Taketo,Felix Beuschlein,Felix Beuschlein,Paula Q. Barrett,Diana L. Carlone,Diana L. Carlone,David T. Breault,David T. Breault +18 more
TLDR
It is shown that rosette formation regulated by β-Catenin and FGFR2 mediate postnatal adrenal cortex zona glomerulosa morphogenesis and is a framework for studying the role of rosettes in adult zonal tissue maintenance and function.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.read more
Citations
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Angiotensin II induces coordinated calcium bursts in aldosterone-producing adrenal rosettes.
Nick A. Guagliardo,Peter M. Klein,Christina A. Gancayco,Adam C Lu,Sining Leng,Rany R. Makarem,Chelsea Cho,Craig G. Rusin,David T. Breault,Paula Q. Barrett,Mark P. Beenhakker +10 more
TL;DR: It is demonstrated that within the rosette, angiotensin II evokes periodic Ca v 3-dependent calcium events that form bursts that are stereotypic in form that define the calcium burst as the fundamental unit of zG layer activity evoked by angiotENSin II and highlight a novel role for the ro sette as a facilitator of cell communication.
Journal ArticleDOI
Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause
Junhua Zhou,Elena A.B. Azizan,Elena A.B. Azizan,Claudia P. Cabrera,Fabio L. Fernandes-Rosa,Sheerazed Boulkroun,Giulia Argentesi,Emily Cottrell,Laurence Amar,Xilin Wu,Sam O’Toole,Emily Goodchild,Alison Marker,Russell Senanayake,Sumedha Garg,Sumedha Garg,Tobias Åkerström,Samuel Backman,Suzanne Jordan,Satyamaanasa Polubothu,Daniel M. Berney,Anna K Gluck,Kate E Lines,Rajesh V. Thakker,Antoinette Tuthill,Caroline Joyce,Juan Pablo Kaski,Fiona E. Karet Frankl,Lou Metherell,Ada E. D. Teo,Mark Gurnell,Laila Parvanta,William Drake,Eva Wozniak,David Klinzing,Jyn Ling Kuan,Zenia Tiang,Zenia Tiang,Celso E Gomez Sanchez,Per Hellman,Roger Foo,Charles A. Mein,Veronica A Kinsler,Peyman Björklund,Helen L Storr,Maria-Christina Zennaro,Morris J. Brown +46 more
TL;DR: In this article, the authors identified gain-of-function mutations in both CTNNB1 and GNA11 by whole-exome sequencing of 3/41 APAs.
Journal ArticleDOI
Wnt/β-catenin activation cooperates with loss of p53 to cause adrenocortical carcinoma in mice.
Kleiton Silva Borges,Kleiton Silva Borges,Kleiton Silva Borges,Emanuele Pignatti,Emanuele Pignatti,Sining Leng,Sining Leng,Dulanjalee Kariyawasam,Dulanjalee Kariyawasam,Gerard Ruiz-Babot,Gerard Ruiz-Babot,Fernando Silva Ramalho,Makoto Mark Taketo,Diana L. Carlone,Diana L. Carlone,David T. Breault,David T. Breault +16 more
TL;DR: This autochthonous model of ACC represents a new tool to investigate the biology of ACC and to identify new treatment strategies and data show that altering both Wnt/β-catenin and p53/Rb signaling is sufficient to drive ACC in mouse.
Journal ArticleDOI
Adrenal cortex development and related disorders leading to adrenal insufficiency.
TL;DR: The development of the adult human adrenal cortex is complex and not fully understood as discussed by the authors, however, the development of this indispensable organ is complex, and it consists of three histologically distinct and functionally specialized zones.
Journal ArticleDOI
Adrenal cortex renewal in health and disease.
Rodanthi Lyraki,Andreas Schedl +1 more
TL;DR: A review integrating advances in the genetic characterization of adrenal diseases and studies of mouse models with altered adrenal phenotypes has helped to elucidate the molecular pathways that regulate adrenal tissue renewal, several of which are fine-tuned via complex paracrine and endocrine influences as discussed by the authors.
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