|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
doi: 10.1242/10.1242/dev.00316
DEVELOPMENT AND DISEASE |
1 Department of Medicine, Division of Endocrinology, Metabolism, and Molecular
Medicine. Northwestern University, Feinberg School of Medicine, Chicago, IL
60611, USA
2 Department of Pathology. Northwestern University, Feinberg School of Medicine,
Chicago, IL 60611, USA
3 Department of Developmental Biology, National Institute for Basic Biology,
Okazaki, Aichi 444-8585, Japan
* Author for correspondence (e-mail: ljameson{at}northwestern.edu)
Accepted 19 November 2002
Mutations of the DAX1 nuclear receptor gene cause adrenal hypoplasia congenita, an X-linked disorder characterized by adrenal insufficiency and hypogonadotropic hypogonadism. Targeted deletion of Dax1 in mice also reveals primary testicular dysgenesis, which is manifest by obstruction of the rete testis by Sertoli cells and hyperplastic Leydig cells, leading to seminiferous tubule dilation and degeneration of germ cells. Because Dax1 is expressed early in gonadal development, and because Sertoli and Leydig cells are located ectopically in the adult, we hypothesized that these testis abnormalities are the result of an early defect in testis development. In Dax1-/Y males, the gonad develops normally until 12.5 dpc. However, by 13.5 dpc, the testis cords are disorganized and incompletely formed in Dax1-deficient mice. The number of germ and Sertoli cells is unchanged, and the expression of Sertoli-specific markers appears to be normal. However, the number of peritubular myoid cells, which normally surround the testis cords, is reduced. BrdU labeling of peritubular myoid cells is low, consistent with decreased proliferation. The basal lamina produced by peritubular myoid and Sertoli cells is disrupted, leading to open and incompletely formed testis cords. Leydig cells, which normally reside in the peritubular space and extend from the coelomic surface to the dorsal surface of the gonad, are restricted to the coelomic surface of Dax1-deficient testis. We conclude that Dax1 plays a crucial role in testis differentiation by regulating the development of peritubular myoid cells and the formation of intact testis cords. The developmental abnormalities in the Dax1-deficient testis lay the foundation for gonadal dysgenesis and infertility in adult mice and, potentially in humans with DAX1 mutations.
Key words: Dax1, Sex differentiation, Gonadal development, Mouse
This article has been cited by other articles:
|
|
 |
|
  Y. Ikeda, H. Tanaka, and M. Esaki Effects of Gestational Diethylstilbestrol Treatment on Male and Female Gonads during Early Embryonic Development Endocrinology, August 1, 2008; 149(8): 3970 - 3979. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.-C. Wu, S. Tomy, and C.-F. Chang The Expression of nr0b1 and nr5a4 During Gonad Development and Sex Change in Protandrous Black Porgy Fish, Acanthopagrus schlegeli Biol Reprod, February 1, 2008; 78(2): 200 - 210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Shoemaker, J. Queen, and D. Crews Response of Candidate Sex-Determining Genes to Changes in Temperature Reveals Their Involvement in the Molecular Network Underlying Temperature-Dependent Sex Determination Mol. Endocrinol., November 1, 2007; 21(11): 2750 - 2763. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. W. Gaido, J. B. Hensley, D. Liu, D. G. Wallace, S. Borghoff, K. J. Johnson, S. J. Hall, and K. Boekelheide Fetal Mouse Phthalate Exposure Shows that Gonocyte Multinucleation is Not Associated with Decreased Testicular Testosterone Toxicol. Sci., June 1, 2007; 97(2): 491 - 503. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. R Manna, Y. Jo, and D. M Stocco Regulation of Leydig cell steroidogenesis by extracellular signal-regulated kinase 1/2: role of protein kinase A and protein kinase C signaling J. Endocrinol., April 1, 2007; 193(1): 53 - 63. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Wilhelm, S. Palmer, and P. Koopman Sex Determination and Gonadal Development in Mammals Physiol Rev, January 1, 2007; 87(1): 1 - 28. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Naciff, K. A. Hess, G. J. Overmann, S. M. Torontali, G. J. Carr, J. P. Tiesman, L. M. Foertsch, B. D. Richardson, J. E. Martinez, and G. P. Daston Gene Expression Changes Induced in the Testis by Transplacental Exposure to High and Low Doses of 17{alpha}-Ethynyl Estradiol, Genistein, or Bisphenol A Toxicol. Sci., August 1, 2005; 86(2): 396 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Bouma, K. H. Albrecht, L. L. Washburn, A. K. Recknagel, G. A. Churchill, and E. M. Eicher Gonadal sex reversal in mutant Dax1 XY mice: a failure to upregulate Sox9 in pre-Sertoli cells Development, July 1, 2005; 132(13): 3045 - 3054. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Liu, K. P. Lehmann, M. Sar, S. S. Young, and K. W. Gaido Gene Expression Profiling Following In Utero Exposure to Phthalate Esters Reveals New Gene Targets in the Etiology of Testicular Dysgenesis Biol Reprod, July 1, 2005; 73(1): 180 - 192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Y. Park, J. J. Meeks, G. Raverot, L. E. Pfaff, J. Weiss, G. D. Hammer, and J. L. Jameson Nuclear receptors Sf1 and Dax1 function cooperatively to mediate somatic cell differentiation during testis development Development, May 15, 2005; 132(10): 2415 - 2423. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Matsuyama, H. Mizusaki, A. Shimono, T. Mukai, K. Okumura, K. Abe, K. Shimada, and K.-i. Morohashi A novel isoform of Vinexin, Vinexin {gamma}, regulates Sox9 gene expression through activation of MAPK cascade in mouse fetal gonad Genes Cells, May 1, 2005; 10(5): 421 - 434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Y. Park and J. L. Jameson Minireview: Transcriptional Regulation of Gonadal Development and Differentiation Endocrinology, March 1, 2005; 146(3): 1035 - 1042. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Suzuki, M. Yagi, K. Saito, and K. Suzuki Dysplastic Development of Seminiferous Tubules and Interstitial Tissue in Rat Hypogonadic (hgn/hgn) Testes Biol Reprod, July 1, 2004; 71(1): 104 - 116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Shima, D. J. McLean, J. R. McCarrey, and M. D. Griswold The Murine Testicular Transcriptome: Characterizing Gene Expression in the Testis During the Progression of Spermatogenesis Biol Reprod, July 1, 2004; 71(1): 319 - 330. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Weiss, J. J. Meeks, L. Hurley, G. Raverot, A. Frassetto, and J. L. Jameson Sox3 Is Required for Gonadal Function, but Not Sex Determination, in Males and Females Mol. Cell. Biol., November 15, 2003; 23(22): 8084 - 8091. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Lalli and P. Sassone-Corsi DAX-1, an Unusual Orphan Receptor at the Crossroads of Steroidogenic Function and Sexual Differentiation Mol. Endocrinol., August 1, 2003; 17(8): 1445 - 1453. [Abstract] [Full Text] [PDF]
|
|
