Division of Endocrinology, Boston Children's Hospital, Boston, MA, 02115, USA.
Division of Medical Sciences, Harvard Medical School, Boston, MA, 02115, USA.
Nat Commun. 2020 Apr 3;11(1):1680. 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.
玫瑰花结在胚胎发育和器官发生过程中的上皮形态发生中被广泛应用。然而，它们在出生后发育和成人组织维持中的作用在很大程度上仍然未知。在这里，我们表明成年肾上腺皮质中的肾小球旁细胞通过黏着连接介导的收缩形成玫瑰花结，并且玫瑰花结的形成是出生后肾上腺肾小球结构成熟的基础。使用遗传小鼠模型，我们表明β-连环蛋白的缺失导致黏着连接的破坏、玫瑰花结数量的减少和肾小球的畸形，而β-连环蛋白的稳定导致黏着连接的丰度增加、玫瑰花结增多和肾小球扩张。此外，我们还发现了大量已知的上皮形态发生调节剂在β-连环蛋白稳定的肾上腺中富集。在这些基因中，我们表明 Fgfr2 通过调节黏着连接的丰度和聚集来调节肾上腺玫瑰花结的形成。总之，我们的数据提供了一个玫瑰花结介导的出生后组织形态发生的例子，并为研究玫瑰花结在成年肾小球旁组织维持和功能中的作用提供了一个框架。
