DAX-1, an ‘antitestis’gene

  title={DAX-1, an ‘antitestis’gene},
  author={Peter N. Goodfellow and Giovanna Camerino},
  journal={Cellular and Molecular Life Sciences CMLS},
Abstract. The DAX-1 gene has been involved in the dosage sensitive sex reversal (DSS) phenotype, a male-to-female sex-reversal syndrome due to the duplication of a small region of human chromosome Xp21. Dax-1 and Sry have been shown to act antagonistically in the mouse system, where increasing expression of the former leads to female development and increasing activity of the latter to male development. Although these data strongly implicate DAX-1 in sex determination, the mouse and human… 

Molecular mechanisms of DAX 1 action

The function ofDAX1 as an antagonist of SF1 in gonadal development is consistent with the fact that in humans, duplication of the region of the X chromosome containing DAX1 causes a similar phenotype as mutations in SF1.

DAX-1, an unusual orphan receptor at the crossroads of steroidogenic function and sexual differentiation.

The mechanism of DAx-1 function in adrenal and gonadal differentiation is reviewed, with special emphasis on recent results showing the critical role of DAX-1 protein misfolding in the pathogenesis of adrenal hypoplasia congenita.

DEVELOPMENT AND DISEASE Dax 1 regulates testis cord organization during gonadal differentiation

DAX1 acts in part by repressing the transcription of other nuclear receptors, including steroidogenic factor 1 (SF1) (Ito et al., 1997), estrogen receptor (Zhang et al. 2000) and androgen receptor (Holter et al, 2002).

Gene dosage of DAX-1, determining in sexual differentiation: duplication of DAX-1 in two sisters with gonadal dysgenesis

This is the first report of 46,XY sex reversal in two siblings who have a maternally inherited duplication of DAX-1 associated with reduced levels of expression of downstream genes as SOX9–SF1.

Targeting DAX-1 in embryonic stem cells and cancer

The past and present milestones in DAX-1 research are reviewed and try to provide hints about the development and fields of application of DAx-1-targeted drugs in the future.

Sox3 Is Required for Gonadal Function, but Not Sex Determination, in Males and Females

It is concluded that Sox3 is not required for gonadal determination but is important for normal oocyte development and male testis differentiation and gametogenesis and targeted mutagenesis to delete Sox3 from mice.

Sox 3 Is Required for Gonadal Function , but Not Sex Determination , in Males and Females

It is concluded that Sox3 is not required for gonadal determination but is important for normal oocyte development and male testis differentiation and gametogenesis and targeted mutagenesis to delete Sox3 from mice.

Up-regulation of WNT-4 signaling and dosage-sensitive sex reversal in humans.

It is shown that, in testicular Sertoli and Leydig cells, Wnt-4 up-regulates Dax1, a gene known to antagonize the testis-determining factor, Sry, which suggests that mammalian sex determination is sensitive to dosage, at multiple steps in its pathway.

Role of Orphan Nuclear Receptor DAX-1/NR0B1 in Development, Physiology, and Disease

The most important findings on the role of DAX-1 in development, physiology, and disease of endocrine tissues since the cloning of its gene twenty years ago are reviewed.



Dax-1 as one of the target genes of Ad4BP/SF-1.

Findings indicate that Ad4BP/SF-1 controls the transcription of the Dax-1 gene, a critical transcription factor in gonadal and adrenal differentiation.

A transcriptional silencing domain in DAX-1 whose mutation causes adrenal hypoplasia congenita.

It is shown that the DAX-1 C terminus contains a potent transcriptional silencing activity, which can be transferred to a heterologous DNA-binding domain, which suggests that transcriptionalsilencing by DAx-1 plays a critical role in the pathogenesis of adrenal hypoplasia congenita.

DNA binding and transcriptional repression by DAX-1 blocks steroidogenesis

In vitro and in vivo evidence is provided that DAX-1 binds DNA and acts as a powerful transcriptional repressor of StAR gene expression, leading to a drastic decrease in steroid production.

Mouse Dax1 expression is consistent with a role in sex determination as well as in adrenal and hypothalamus function

The isolation of the mouse Dax1 gene and its pattern of expression during development suggest a basis for adrenal insufficiency and hypogonadotropic hypog onadotropicism in males affected by adrenal hypoplasia congenita and are consistent with a role for DAX1 in gonadal sex determination.

Identification of a putative steroidogenic factor-1 response element in the DAX-1 promoter.

It is demonstrated thatSF-1 is able to efficiently bind to the putative SF-1 response element found in the DAX-1 promoter in vitro, which suggests that SF- 1 may directly regulate the expression of DAx-1 and that these two transcription factors may be components of a cascade required for development of steroidogenic tissues.

Dax1 antagonizes Sry action in mammalian sex determination

Results show that DAX1 is largely, if not solely, responsible for dosage-sensitive sex reversal and provide a model for early events in mammalian sex determination, when precise levels and timing of gene expression are critical.

DAX-1 inhibits SF-1-mediated transactivation via a carboxy-terminal domain that is deleted in adrenal hypoplasia congenita

It is concluded that DAX-1 can inhibit SF-1 transcriptional activity and suggested that the loss of this inhibitory property in DAx-1 may account in part for the phenotype of AHC.

The Wilms’ Tumor Suppressor Gene (wt1) Product Regulates Dax-1 Gene Expression during Gonadal Differentiation

The results indicate that the WT1–DAX-1 pathway is an early event in the process of mammalian sex determination, and it is suggested that WT1 regulates Dax-1via GC-rich binding sites found upstream of the DX1 TATA box.