Abstract
DAX-1/NR0B1 is an unusual orphan receptor that has a pivotal role in the development and function of steroidogenic tissues and of the reproductive axis. Recent studies have also indicated that this transcription factor has an important function in stem cell biology and in several types of cancer. Here I critically review 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.
Highlights
Nuclear hormone receptors are intracellular proteins that are responsible for sensing lipophilic substances and mediating their physiological actions, directly regulating the expression of target genes through binding to DNA
In a further study analyzing Dax1 protein expression, Ikeda et al reported a more complex pattern of Dax-1 expression in the developing mouse gonads, with levels gradually decreasing in the testis until E16.5 and increasing again at E18.5, while Dax-1 expression in the ovary continues to be high until E14.5 but significantly decreased at E16.5 and E18.5 [17]
All these results argue against the previously advanced model that a sexual dimorphism of Dax-1 expression during gonad development is required for ovarian differentiation and rather suggest that this transcription factor has a specific function in different cell types in both sexes
Summary
Nuclear hormone receptors are intracellular proteins that are responsible for sensing lipophilic substances and mediating their physiological actions, directly regulating the expression of target genes through binding to DNA. Nuclear receptors are implicated in a large variety of biological processes and have a special importance in development and endocrine functions (reviewed in [1]). Ligands are not known for all family members: the terminology of “orphan” is used to indicate those proteins, which often possess a defined transcriptional function in the apparent absence of ligands. This spotlight paper is focused on a peculiar orphan receptor, DAX-1 (NR0B1 in the nuclear receptor official nomenclature), and will review the most important findings about its role in development, physiology, and disease
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