Targeted disruption of β-catenin in Sf1-expressing cells impairs development and maintenance of the adrenal cortex

Abstract

high, a transgene expressed at high levels, caused adrenal aplasia in newborn mice. Analysis of fetal adrenal development with Sf1/Cre high -mediated β-catenin inactivation showed decreased proliferation in presumptive adrenocortical precursor cells. By contrast, the Sf1/Cre low transgene effected a lesser degree of β-catenin inactivation that did not affect all adrenocortical cells, permitting adrenal survival to reveal age-dependent degeneration of the cortex. These results define crucial roles for β-catenin -presumably as part of the Wnt canonical signaling pathway -in both embryonic development of the adrenal cortex and in maintenance of the adult organ.

Adrenal cortical and chromaffin stem cells: Is there a common progeny related to stress adaptation?

“…Since Nestin expression can be related to malignancy and an undifferentiated state of the tumor this suggests that Nestin expression can be the consequence of a failure in certain key regulatory pathways in the stem cells (Krupkova et al, 2010). For example, adrenocortical tumors have been suggested to arise from a Wnt/β-catenin dysregulation (Simon and Hammer, 2012), which is not surprising as the activation of the Wnt/β-catenin pathway is crucial for adrenal development and homeostatic maintenance of the gland (Kim et al, 2008).…”

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

“…Several lines of evidence suggest that β-catenin plays an important role in adrenal zonation and maintenance. Activation of the β-catenin pathway is restricted to the ZG (Kim et al 2008;Walczak et al 2014), and ectopic expression leads to the activation of ZG markers in ZF cells (Berthon et al 2010). Moreover, β-catenin seems to bind to and control the expression of At1r, a gene specifically expressed within the ZG (Berthon et al 2014).…”

“…Moreover, β-catenin seems to bind to and control the expression of At1r, a gene specifically expressed within the ZG (Berthon et al 2014). Finally, stochastic deletion of β-catenin using a low-level expressing Sf1-Cre line leads to progressive loss of the adrenal cortex in adult life (Kim et al 2008).…”

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

“…-catenin is a multifunctional protein with one of its main functions being to act as a transcriptional cofactor for members of the Lef/Tcf family of transcription factors. In this capacity, -catenin acts as a final downstream target of the action of the Wnt family of secreted signalling molecules (for an in depth review of this pathway read [75]) A role for -catenin in adrenal development has recently been demonstrated by the study of mice with a conditional allele of this gene and a transgene containing Cre recombinase driven by Sf1 regulatory sequences [76]. In this study two transgenic Cre lines were used: one carried one copy of the transgene and had low recombination efficiency in the adrenal cortex (Sf1/Cre Low ); the other line carried five copies of the same transgene and displayed high recombination efficiency (Sf1/Cre High ).…”

“…-catenin has been shown to play important roles in progenitor cell expansion and lineage decisions in multiple tissues [77]. In the adult adrenal,-catenin was found to be expressed in the subcapsular area [76] which has been postulated to contain adrenal progenitor cells [78]. It is thus tempting to speculate that -catenin plays a role in renewal and/or commitment of progenitors, in order to maintain adrenal cortical function throughout life.…”