Dax1 regulates testis cord organization during gonadal differentiation

Joshua J. Meeks, Susan E. Crawford, Theron A. Russell, Ken Ichiro Morohashi, Jeffrey Weiss, J. Larry Jameson

Research output: Contribution to journalReview article

103 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1029-1036
Number of pages8
JournalDevelopment
Volume130
Issue number5
DOIs
Publication statusPublished - Mar 1 2003

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Testis
Sertoli Cells
Leydig Cells
Gonads
Germ Cells
Rete Testis
Gonadal Dysgenesis
Adrenal Insufficiency
Mutation
Seminiferous Tubules
Hypogonadism
Bromodeoxyuridine
Cytoplasmic and Nuclear Receptors
Basement Membrane
Infertility
Dilatation
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

Cite this

Meeks, J. J., Crawford, S. E., Russell, T. A., Morohashi, K. I., Weiss, J., & Jameson, J. L. (2003). Dax1 regulates testis cord organization during gonadal differentiation. Development, 130(5), 1029-1036. https://doi.org/10.1242/dev.00316

Dax1 regulates testis cord organization during gonadal differentiation. / Meeks, Joshua J.; Crawford, Susan E.; Russell, Theron A.; Morohashi, Ken Ichiro; Weiss, Jeffrey; Jameson, J. Larry.

In: Development, Vol. 130, No. 5, 01.03.2003, p. 1029-1036.

Research output: Contribution to journalReview article

Meeks, JJ, Crawford, SE, Russell, TA, Morohashi, KI, Weiss, J & Jameson, JL 2003, 'Dax1 regulates testis cord organization during gonadal differentiation', Development, vol. 130, no. 5, pp. 1029-1036. https://doi.org/10.1242/dev.00316
Meeks JJ, Crawford SE, Russell TA, Morohashi KI, Weiss J, Jameson JL. Dax1 regulates testis cord organization during gonadal differentiation. Development. 2003 Mar 1;130(5):1029-1036. https://doi.org/10.1242/dev.00316
Meeks, Joshua J. ; Crawford, Susan E. ; Russell, Theron A. ; Morohashi, Ken Ichiro ; Weiss, Jeffrey ; Jameson, J. Larry. / Dax1 regulates testis cord organization during gonadal differentiation. In: Development. 2003 ; Vol. 130, No. 5. pp. 1029-1036.
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