Fgfr2 is required for the expansion of the early adrenocortical primordium

Häfner, Regine; Bohnenpoll, Tobias; Rudat, Carsten; Schultheiss, Thomas M.; Kispert, Andreas

doi:10.1016/j.mce.2015.06.022

Cited by 21 publications

(12 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our single molecule in situ hybridization data show that the expression domain of Fgfr2 overlaps with the area of Wnt activation, namely the zG in control and the expanded zG in βCat-GOF adrenals. This is consistent with previous reports showing that the Fgfr2 expression pattern in the fetal adrenal is localized to the outer cortex, where Wnt/β-catenin signaling is active 29,60,61 . During neuromast assembly in the lateral line primordium of zebrafish, FGF signaling plays an essential role in rosette formation by triggering Shroom3-mediated apical constriction 16 .…”

Section: Discussionsupporting

confidence: 93%

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

et al. 2020

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 93%

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

et al. 2020

View full text Add to dashboard Cite

show abstract

“… 45 , 46 ), Tbx18 (refs. 47 , 48 ), or steroidogenic factor 1 ( Sf1 ) 49 ) have shown that following these events, the basement membrane underneath the coelomic epithelium disintegrates, which allows the proliferating cells of the coelomic epithelium to undergo EMT, and to ingress and form a cluster of SF1 + gonadal somatic precursor cells 50 , 51 , which later give rise to the supporting Sertoli cells of the testis cords and seminiferous tubules 52 , 53 , or the follicular (or granulosa) cells of the ovarian follicles 54 , 55 . The supporting cells are not the only cells derived from the coelomic epithelium in the primitive gonads of mice.…”

Section: Mesothelial Cell Emt Involvement In Healthy Organ Developmenmentioning

confidence: 99%

“…The supporting cells are not the only cells derived from the coelomic epithelium in the primitive gonads of mice. Cell-tracking experiments have shown that the SF1 + gonadal precursor cells generate the testicular peritubular myoid cells (PMCs, the smooth muscle cells surrounding the seminiferous tubules in the testis) through EMT and the steroidogenic Leydig cells and Theca cells in testis and ovaries, respectively 44 , 46 – 48 , 53 , 56 – 58 . The molecular mechanisms driving coelomic epithelium transformation into the genital ridge have not been laid out as comprehensively as for the embryonic heart or liver, but a similar gene signature in gonadal tissues can be observed around this time.…”

Section: Mesothelial Cell Emt Involvement In Healthy Organ Developmenmentioning

confidence: 99%

Mesothelial to mesenchyme transition as a major developmental and pathological player in trunk organs and their cavities

Koopmans

Rinkevich

2018

Commun Biol

View full text Add to dashboard Cite

The internal organs embedded in the cavities are lined by an epithelial monolayer termed the mesothelium. The mesothelium is increasingly implicated in driving various internal organ pathologies, as many of the normal embryonic developmental pathways acting in mesothelial cells, such as those regulating epithelial-to-mesenchymal transition, also drive disease progression in adult life. Here, we summarize observations from different animal models and organ systems that collectively point toward a central role of epithelial-to-mesenchymal transition in driving tissue fibrosis, acute scarring, and cancer metastasis. Thus, drugs targeting pathways of mesothelium’s transition may have broad therapeutic benefits in patients suffering from these diseases.

show abstract

“…FGFR2 signalling increases proliferation and acts as a negative regulator of apoptosis in adrenocortical precursor cells [9]. Recent studies also identified aberrant FGFR2 signalling as an important factor in oncogenesis and as a potential drug target in different cancer types [10].…”

Section: Introductionmentioning

confidence: 99%

Subcellular localization of fibroblast growth factor receptor type 2 and correlation with CTNNB1 genotype in adrenocortical carcinoma

Thiel

Scholl

Ashmawy

et al. 2020

Preprint

View full text Add to dashboard Cite

Objective: Fibroblast growth factor receptor (FGFR)2 regulates the development of the adrenal gland in mice. In addition, FGFR2-mediated signalling has been shown to prevent apoptosis and to enhance proliferation in adrenocortical precursor cells. The activation of the Wingless/Int-1 (WNT) / beta catenin pathway as a key mechanism of adrenocortical tumourigenesis has been linked to FGFR2 signalling in other cell types. Therefore we hypothesised that FGFR2 expression may also play a role in adrenocortical carcinoma (ACC). We conducted a pilot study and analysed protein expression of FGFR2 in 26 ACCs using immunohistochemistry technique. Data on the CTNNB1 mutation status and clinical data were correlated to the expression of FGFR2. Results: We observed a high variability in FGFR2 expression between the different tumour samples. There was a subset of ACC with comparatively high nuclear expression of FGFR2. We did not find a clear association between the CTNNB1 mutational status or clinical features and the FGFR2 expression. We conclude that FGFR signalling plays a role in adrenocortical carcinoma. Our data encourages further investigations of FGFR signalling in ACC, especially since new inhibitors of FGFR signalling are already entering clinical trials for the treatment of other cancer types.

show abstract

Fgfr2 is required for the expansion of the early adrenocortical primordium

Cited by 21 publications

References 56 publications

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

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

Mesothelial to mesenchyme transition as a major developmental and pathological player in trunk organs and their cavities

Subcellular localization of fibroblast growth factor receptor type 2 and correlation with CTNNB1 genotype in adrenocortical carcinoma

Contact Info

Product

Resources

About