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Open AccessJournal ArticleDOI

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

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.

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Angiotensin II induces coordinated calcium bursts in aldosterone-producing adrenal rosettes.

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

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.
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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.

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.
References
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Journal ArticleDOI

Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

TL;DR: This work presents DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates, which enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression.
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STAR: ultrafast universal RNA-seq aligner

TL;DR: The Spliced Transcripts Alignment to a Reference (STAR) software based on a previously undescribed RNA-seq alignment algorithm that uses sequential maximum mappable seed search in uncompressed suffix arrays followed by seed clustering and stitching procedure outperforms other aligners by a factor of >50 in mapping speed.
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featureCounts: an efficient general-purpose program for assigning sequence reads to genomic features

TL;DR: FeatureCounts as discussed by the authors is a read summarization program suitable for counting reads generated from either RNA or genomic DNA sequencing experiments, which implements highly efficient chromosome hashing and feature blocking techniques.
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Junctional complexes in various epithelia

TL;DR: The tight junction is impervious to concentrated protein solutions and appears to function as a diffusion barrier or "seal," and the desmosome and probably also the zonula adhaerens may represent intercellular attachment devices.
Journal ArticleDOI

Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities.

TL;DR: The core Wnt/β-catenin signaling pathway is described, how it controls stem cells, and contributes to disease, and strategies for Wnt-based therapies are discussed.
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