Nr0b1, also known as DAX1, is a nuclear receptor gene encoding a transcriptional factor that plays a key role in adrenal and reproductive development in vertebrates [3,5,7,8]. It is involved in multiple biological processes, such as neural progenitor regulation, sex determination, and cell survival regulation, potentially through its influence on pathways like Notch signaling [1,9].

In zebrafish, nr0b1 disruption causes abnormal hypothalamic functions, including abnormal gonadotropin expression, changes in fertilization rate and post-fasting food intake. Loss of nr0b1 leads to an altered number of specific neurons in the hypothalamic arcuate region, along with reduced progenitor cell proliferation and decreased Notch pathway gene expression [1]. In the same species, nr0b1 mutation results in female-to-male sex reversal due to abnormal gonadal proliferation and differentiation [9]. In lung cancer cells, NR0B1 depletion restrains xenograft tumor growth and facilitates ferroptosis, while in hepatocellular carcinoma, NR0B1 promotes autophagy, inhibits apoptosis, and augments sorafenib resistance [2,6]. Also, in humans, NR0B1 mutations are associated with congenital adrenal hyperplasia, X-linked adrenal hypoplasia congenita, and hypogonadotropic hypogonadism [3,4,5,7,8].

In summary, Nr0b1 is crucial for normal hypothalamic neuron development, sex development, and is involved in various disease-related processes such as cancer cell survival and ferroptosis regulation. Studies in genetic models like zebrafish have significantly contributed to understanding Nr0b1's functions and its role in diseases like adrenal and reproductive disorders [1,3,4,5,6,7,8,9].