The adrenal capsule is a signaling center controlling cell renewal and zonation through <i>Rspo3</i>

Vidal, Valérie; Sacco, Sonia; Rocha, Ana Sofia; Silva, Fabio da; Panzolini, Clara; Dumontet, Typhanie; Doan, Thi Mai Phuong; Shan, Jingdong; Rak-Raszewska, Aleksandra; Bird, Tom; Vainio, Seppo; Martinez, Antoine; Schedl, Andreas

doi:10.1101/gad.277756.116

Cited by 87 publications

(105 citation statements)

References 31 publications

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“…We extracted expression levels of a list of 28 genes expressed or functionally linked to the progenitor compartment and found that 18 of them were significantly (t test, adjusted P < 0.05) downregulated in Prkar1a-knockout adrenals compared with WT adrenals (Supplemental Figure 4B). We further confirmed by qPCR that Prkar1a ablation in steroidogenic cells resulted in the downregulation of all stem/progenitor markers (12,14,(41)(42)(43) from either capsular or subcapsular compartments (Supplemental Figure 4C). The SHH and RSPO/WNT/β-catenin signaling pathways play an essential role in adult cortex maintenance and renewal (12,14).…”

Section: Pka-dependent Accelerated Cortex Renewal Is Counteracted Bysupporting

confidence: 54%

“…We further confirmed by qPCR that Prkar1a ablation in steroidogenic cells resulted in the downregulation of all stem/progenitor markers (12,14,(41)(42)(43) from either capsular or subcapsular compartments (Supplemental Figure 4C). The SHH and RSPO/WNT/β-catenin signaling pathways play an essential role in adult cortex maintenance and renewal (12,14). Interestingly, even though the mutant cortex was fully recombined by 3 months, expression of Shh, Gli1, Wnt4, and Rspo3 was unaltered at this stage in DAdKO female adrenals; however, we observed a 50% decrease in their expression at 7 months (Supplemental Figure 4D).…”

Section: Pka-dependent Accelerated Cortex Renewal Is Counteracted Bysupporting

confidence: 54%

“…In the adult cortex, WNT and PKA signaling pathways play essential and complementary roles in functional zonation. Gain-and loss-of-function models have shown that the RSPO/WNT/β-catenin pathway is a driver of zG identity, a repressor of zF identity, and has tumorigenic activity when constitutively activated (14)(15)(16)(17). Reciprocally, constitutive activation of cAMP/PKA signaling was shown to inhibit zG fate, trigger zF identity, and counteract β-catenin-induced tumorigenesis (18,19).…”

Section: Introductionmentioning

confidence: 99%

“…This process eventually induces differentiation of progenitors into zG cells that are pushed in a centripetal fashion and converted into zF cells (11)(12)(13)(14). Stem/progenitor reservoirs are themselves maintained through reciprocal signals, among which Rspo3 induces Wnt4 and Shh expression within steroidogenic cells and Shh in turn signals back to recruit capsular cells (14).…”

Section: Introductionmentioning

confidence: 99%

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PKA signaling drives reticularis differentiation and sexually dimorphic adrenal cortex renewal

Dumontet¹,

Sahut‐Barnola²,

Septier³

et al. 2018

JCI Insight

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Section: Pka-dependent Accelerated Cortex Renewal Is Counteracted Bysupporting

confidence: 54%

Section: Pka-dependent Accelerated Cortex Renewal Is Counteracted Bysupporting

confidence: 54%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

PKA signaling drives reticularis differentiation and sexually dimorphic adrenal cortex renewal

Dumontet¹,

Sahut‐Barnola²,

Septier³

et al. 2018

JCI Insight

Self Cite

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“…Studies have demonstrated the importance of the adrenal capsule in the control of adrenocortical cell renewal and zonation (15, 18). More recently, PKA and ACTH signaling have been implicated in the regulation of adrenal zonation determining the ZG/ZF border (23). …”

Section: Resultsmentioning

confidence: 99%

MRAP deficiency impairs adrenal progenitor cell differentiation and gland zonation

et al. 2018

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Melanocortin 2 receptor accessory protein (MRAP) is a single transmembrane domain accessory protein and a critical component of the hypothamo-pituitary-adrenal axis. MRAP is highly expressed in the adrenal gland and is essential for adrenocorticotropin hormone (ACTH) receptor expression and function. Human loss-of-function mutations in MRAP cause familial glucocorticoid (GC) deficiency (FGD) type 2 (FGD2), whereby the adrenal gland fails to respond to ACTH and to produce cortisol. In this study, we generated Mrap-null mice to study the function of MRAP in vivo. We found that the vast majority of Mrap−/− mice died at birth but could be rescued by administration of corticosterone to pregnant dams. Surviving Mrap−/− mice developed isolated GC deficiency with normal mineralocorticoid and catecholamine production, recapitulating FGD2. The adrenal glands of adult Mrap−/− mice were small, with grossly impaired adrenal capsular morphology and cortex zonation. Progenitor cell differentiation was significantly impaired, with dysregulation of WNT4/β-catenin and sonic hedgehog pathways. These data demonstrate the roles of MRAP in both steroidogenesis and the regulation of adrenal cortex zonation. This is the first mouse model of isolated GC deficiency and reveals the role of MRAP in adrenal progenitor cell regulation and cortex zonation.—Novoselova, T. V., Hussain, M., King, P. J., Guasti, L., Metherell, L. A., Charalambous, M., Clark, A. J. L., Chan, L. F. MRAP deficiency impairs adrenal progenitor cell differentiation and gland zonation.

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Post‐hatching developmental changes in the adrenal gland of the Japanese quail (Coturnix coturnix japonica): Histological, immunohistochemical, and electron microscopic studies

Abdel-Maksoud

Abou-Elmagd

Saleh

2023

Microscopy Res & Technique

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The adrenal glands are paired abdominal endocrine organs vital to the bird's health. The present research aimed to provide a comprehensive examination of the histological, ultrastructural, and immunohistochemical investigations of the adrenal gland in Japanese quail during the post hatching period. The current study was performed on 21 healthy Japanese quail chicks at different post hatching periods. Our results showed the adrenal gland is surrounded by a connective tissue capsule, which consists of dense collagen fibers containing large blood vessels, chromaffin cells, autonomic ganglia, fibroblasts, and migrating Schwann cells. The zonation of the adrenal gland is composed of a subcapsular layer, a peripheral zone, and a central zone, which gets more pronounced with age. At the ultrastructural level, the interrenal cells take the steroid‐secreting cells characters; they have varying amounts of lipid droplets and abundant mitochondria. Adrenal medullary chromaffin cells showed positive immunoreactivity to the NSE. With increasing age, the chromaffin tissue's Sox10 immunoreactivity increased. β‐catenin is expressed within the plasmalemma and the cytoplasm of the interrenal and chromaffin cells and its reactivity increased with age, especially in the chromaffin cells. Our results indicate the adrenal gland undergoes significant morphological changes during the postnatal life. Overall, the postnatal period is an important time for the development and maturation of the adrenal glands.

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The adrenal capsule is a signaling center controlling cell renewal and zonation through Rspo3

Cited by 87 publications

References 31 publications

PKA signaling drives reticularis differentiation and sexually dimorphic adrenal cortex renewal

PKA signaling drives reticularis differentiation and sexually dimorphic adrenal cortex renewal

MRAP deficiency impairs adrenal progenitor cell differentiation and gland zonation

Post‐hatching developmental changes in the adrenal gland of the Japanese quail (Coturnix coturnix japonica): Histological, immunohistochemical, and electron microscopic studies

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