Gene dosage effects and transcriptional regulation of early mammalian adrenal cortex development

Val, Pierre; Swain, Amanda

doi:10.1016/j.mce.2009.12.010

Cited by 21 publications

(12 citation statements)

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“…NR5A1 encodes the nuclear receptor family member nuclear receptor subfamily 5 group A member 1, also known as steroidogenic factor-1 (SF1), which plays a role in gonadal and adrenal development (Val and Swain 2010). NR5A1 is expressed in the urogenital ridge, the developing hypothalamus, and the anterior pituitary gland.…”

Section: Genes Required For the Development Of The Bi-potential Gonadmentioning

confidence: 99%

Mammalian sex determination—insights from humans and mice

2012

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Disorders of sex development (DSD) are congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical. Many of the genes required for gonad development have been identified by analysis of DSD patients. However, the use of knockout and transgenic mouse strains have contributed enormously to the study of gonad gene function and interactions within the development network. Although the genetic basis of mammalian sex determination and differentiation has advanced considerably in recent years, a majority of 46,XY gonadal dysgenesis patients still cannot be provided with an accurate diagnosis. Some of these unexplained DSD cases may be due to mutations in novel DSD genes or genomic rearrangements affecting regulatory regions that lead to atypical gene expression. Here, we review our current knowledge of mammalian sex determination drawing on insights from human DSD patients and mouse models.

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Section: Genes Required For the Development Of The Bi-potential Gonadmentioning

confidence: 99%

Mammalian sex determination—insights from humans and mice

2012

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“…In this review we focus on recent advances in defining the roles during adrenocortical development of the intercellular signal Sonic hedgehog, and the signaling pathway through which it acts, based primarily on data from mouse models. For more comprehensive reviews of the transcription factors and other signals involved in adrenal development see (Else and Hammer, 2005; Kim and Hammer, 2007; Val and Swain, 2010; Morohashi and Zubair, 2011; Wakil and Lalli, 2011). …”

Section: Introductionmentioning

confidence: 99%

Sonic hedgehog signaling during adrenal development

Laufer

Kesper

Vortkamp

et al. 2012

Molecular and Cellular Endocrinology

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It has been speculated for a number of years that Sonic hedgehog (Shh) signaling plays an important role in adrenal development. Over the past two years several reports have described the expression and function of Shh pathway genes in the adrenal cortex, using primarily mouse models. The key findings are that Shh signals produced by a population of partially differentiated cortical cells located in the outer cortex/zona glomerulosa are received by non-cortical mesenchymal cells located predominantly in the overlying capsule. This signal is required for growth of both the capsule and the cortex, but not for cortical zonation or steroidogenic cell differentiation. Using molecular genetic tools to define the adrenocortical cell lineages that are descended from both Shh signaling and receiving cells, both capsule and cortical cells were found to have properties of adrenocortical stem and/or progenitor cells. Here we place these observations within the context of prior studies on adrenal development, postnatal adrenal maintenance and adrenocortical stem/progenitor cell lineages.

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“…In mice these zones include an outer zona glomerulosa (ZG) that produces mineralocorticoids, a more central zona fasciculata (ZF) that produces glucocorticoids, and a transient fetal/X-zone of indeterminate function that is present embryonically and in immature animals but regresses at sexual maturity in males, and at the first pregnancy in females (Kim et al, 2009; Val and Swain, 2010). …”

Section: Introductionmentioning

confidence: 99%

“…Mature ZG cells express zonally-restricted Cyp11B2 as well as SF1 and scc, but most do not express Shh . ZF cells express pan-steroidogenic markers and Cyp11B1 but not Shh or Cyp11B2 (Domalik et al, 1991; Hatano et al, 1994; King et al, 2009; Luo et al, 1994; Val and Swain, 2010). Fetal/X-zone cells express SF1 and scc, as well as the zonal marker 20-alpha-hydroxysteroid dehydrogenase (20aHSD; Hershkovitz et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…Molecular genetic analyses have begun to characterize the lineage relationships among these different cell populations, as well as the functional consequences of mutating various signaling molecules, transcription factors and ion channels (Ching and Vilain, 2009; Davies et al, 2008; Heitzmann et al, 2008; Huang et al, 2010; Kim et al, 2009; Kim et al, 2008; King et al, 2009; Val and Swain, 2010; Zubair et al, 2008). Interpreting the phenotypes in these experiments at the cellular level is greatly facilitated by the ability to assess the expression of multiple markers simultaneously, most effectively using multichannel fluorescence microscopy, where three or four markers, often detected immunologically, can simultaneously be assessed.…”

Section: Introductionmentioning

confidence: 99%

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Endogenous biotin as a marker of adrenocortical cells with steroidogenic potential

Paul

Laufer

2011

Molecular and Cellular Endocrinology

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Interpretation of adrenal cortex phenotypes is greatly facilitated by simultaneous examination of multiple markers at single cell resolution. However the availability of multiple appropriate antibodies can be rate limiting, while their cognate antigens are often subject to variable accessibility. Specific markers not subject to these constraints thus have obvious utility. Here we report that endogenous biotin, when detected in fixed, frozen tissue sections using fluorescent streptavidin, is a specific marker of apparently all cells with steroidogenic potential in the murine adrenal cortex. While streptavidin stains presteroidogenic and mature cortical cells, it does not label the adrenal capsule, medulla or vascular endothelium. Developmental profiles reveal adrenal endogenous biotin labeling from E13.5 through adulthood. Comparisons with zonal markers, hypothalamic-pituitary-adrenal (HPA) axis-remodeled tissue, transgenic Shhn-LacZ or Gli1-nLacZ animals, and Shh mutant embryos further demonstrate the utility of this approach. Fluorescent streptavidin applied using a simple one-step staining protocol thus provides a potent counterstain for use in adrenal analyses.

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Gene dosage effects and transcriptional regulation of early mammalian adrenal cortex development

Abstract: International audienc

Cited by 21 publications

References 123 publications

Mammalian sex determination—insights from humans and mice

Mammalian sex determination—insights from humans and mice

Sonic hedgehog signaling during adrenal development

Endogenous biotin as a marker of adrenocortical cells with steroidogenic potential

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