ARX/Arx is expressed in germ cells during spermatogenesis in both marsupial and mouse

Abstract

The X-linked aristaless gene, ARX, is essential for the development of the gonads, forebrain, olfactory bulb, pancreas, and skeletal muscle in mice and humans. Mutations cause neurological diseases, often accompanied by ambiguous genitalia. There are a disproportionately high number of testis and brain genes on the human and mouse X chromosomes. It is still unknown whether the X chromosome accrued these genes during its evolution or whether genes that find themselves on the X chromosome evolve such roles. ARX was originally autosomal in mammals and remains so in marsupials, whereas in eutherian mammals it translocated to the X chromosome. In this study, we examined autosomal ARX in tammars and compared it with the X-linked Arx in mice. We detected ARX mRNA in the neural cells of the forebrain, midbrain and hindbrain, and olfactory bulbs in developing tammars, consistent with the expression in mice. ARX was detected by RT-PCR and mRNA in situ hybridization in the developing tammar wallaby gonads of both sexes, suggestive of a role in sexual development as in mice. We also detected ARX/Arx mRNA in the adult testis in both tammars and mice, suggesting a potential novel role for ARX/Arx in spermiogenesis. ARX transcripts were predominantly observed in round spermatids. Arx mRNA localization distributions in the mouse adult testis suggest that it escaped meiotic sex chromosome inactivation during spermatogenesis. Our findings suggest that ARX in the therian mammal ancestor already played a role in male reproduction before it was recruited to the X chromosome in eutherians.

DAX1/NR0B1 Was Expressed During Mammalian Gonadal Development and Gametogenesis Before It Was Recruited to the Eutherian X Chromosome1

“…Furthermore, it suggests that this role for NR0B1 in Sertoli cell function existed before it was relocated to the X chromosome. This is similar to the pattern observed in other marsupial-autosomal/eutherian X-linked genes, ARX and TGIF [51,52], which both evolved roles in Sertoli cell function and male reproduction before their recruitment to the X chromosome.…”

“…The abundant staining of NR0B1 in these late-stage germ cells in mice indicates either that the protein persists from existing reservoirs created prior to MSCI, or that NR0B1 can escape MSCI. This is similar to the pattern seen in the eutherian ARX gene, which also has an autosomal origin in mammals [51]. Despite the highly conserved distribution of germ cell NR0B1 during spermatogenesis, its functional significance in these cells is unknown.…”

Regulating transcriptional activity by phosphorylation: A new mechanism for the ARX homeodomain transcription factor

“…Interestingly, PICK1 is expressed in many tissues with the highest expression found in the brain, followed by the testis (15). These are both sites in which ARX is also expressed [ 27 , 28 ]. PICK1 is known to be localised to the cytoplasmic region of cells, in particular, the perinuclear region and associates with the mitochondria.…”

The role of DNA methylation in the pathogenesis of type 2 diabetes mellitus

“…The aristaless-related homeobox ( ARX ) gene is an X-linked transcription factor that functions in humans and mice to regulate the development of the pancreas among various other tissues. In the mouse pancreas, Arx has been found to be expressed throughout all stages of pancreatic development [ 19 ]. As such, Arx is first observed in the pancreatic anlage, followed by the differentiating precursors of the pancreatic endocrine cells and, finally, the ensuing α cells [ 20 ].…”