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  • Review Article
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One tissue, two fates: molecular genetic events that underlie testis versus ovary development

Nature Reviews Genetics volume 5, pages 509–521 (2004)Cite this article

Key Points

  • The gonad arises as a bipotential organ primordium. Expression of the Y-linked gene, Sry, in the bipotential gonad leads to the differentiation of Sertoli cells, which orchestrate testis development.

  • SRY is a high-mobility group (HMG)-type DNA-binding protein that might act as a classic transcription factor, or might be involved in regulating chromatin.

  • Establishment of the testis pathway requires proliferation of the pre-Sertoli-cell population and maintenance of Sox9 in the Sertoli-cell nucleus, both of which depend on Fgf9 signalling.

  • Migration of endothelial and peri-endothelial cells from the mesonephros into the gonad occurs specifically in XY gonads, gives rise to the arterial system in the testis and is required for testis-cord formation.

  • Fetal Leydig-cell development in the testis requires the DHH and PDGF signalling pathways, as well as the non-cell-autonomous activity of the aristaless-related homeobox gene, Arx.

  • XX or XY germ cells differentiate on the basis of their somatic-cell environment: in an XY environment, they arrest in G0–G1 of mitosis, whereas in an XX environment, they spontaneously enter meiosis and might suppress male development.

  • Several new genes that are specific to the ovarian pathway have been identified, and genomic and mutagenesis methods promise to reveal many more players in both male and female pathways in the near future.

Abstract

The pivotal point of vertebrate sex determination is the development of the gonad into a testis or ovary, which governs phenotypic sex through the production of hormones. The identification of Sry, the genetic switch that controls testis development in mammals, fuelled the race for the discovery of downstream pathways. Comparative analyses of XY versus XX gonadogenesis in both mouse and human genetic mutants have uncovered a burgeoning network of intra- and extra-cellular pathways. Here, we review the old and new players that are involved in the initial steps of testis and ovary development.

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Figure 1: Genetic pathways with a characterized functional role in the divergent development of XX and XY gonads.
Figure 2: Compartmentalization of the testis.
Figure 3: XY-specific proliferation of coelomic epithelial cells.
Figure 4: Cellular events downstream of Sry rapidly organize testis structure.

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Acknowledgements

We would like to thank past and present members of the laboratory for images that appear in figure 4. We also thank members of this laboratory and other colleagues for their thoughtful contributions to this Review and for data in advance of publication. This work is supported by grants from the National Institutes of Health and the National Science Foundation to B.C.

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Authors and Affiliations

  1. Department of Cell Biology, Duke University Medical Center, Durham, 27710, North Carolina, USA

    Jennifer Brennan & Blanche Capel

  2. Department of Genetics, University of North Carolina, Chapel Hill, 27599, North Carolina, USA

    Jennifer Brennan

Authors
  1. Jennifer Brennan
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  2. Blanche Capel
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Correspondence to Blanche Capel.

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DATABASES

Entrez

Amh

Arx

ATRX

Bmp2

Dax1

Dhh

Dmrt1

Emx2

Fgf9

FGFR2

Fog2

Foxl2

Fst

Gata4

Gcl

Gcna1

Igf1r

Ir

Irr

Kit

Lhx9

Mis

M33

Mvh

Ods

Pdgfrα

Pisrt1

Ptch1

Sf1

Sox3

Sox8

Sox9

Stra8

Sry

Tnap

TrkA

TrkC

Wnt4

Wt1

FURTHER INFORMATION

Blanche Capel's laboratory

Glossary

PRIMORDIA

The initial founder group of cells that give rise to a tissue.

COELOMIC EPITHELIUM

An epithelial layer that lines the coelom, the body cavity, and covers the abdominal organs that arise beneath it.

MESONEPHROS

The mid-region of the embryonic kidney that arises within the intermediate mesoderm between the pronephros and the metanephros (the definitive kidney). The gonad develops on the medial surface of this transient tissue, which also houses the primordia for the male (mesonephric) and female (Müllerian) ducts.

PERITUBULAR MYOID CELLS

A muscle-lineage cell type that surrounds the Sertoli-cell cords and is believed to be responsible for peristaltic action that is involved in the expulsion of sperm from the seminiferous tubules.

LEYDIG CELLS

Interstitial cells in the testis that are responsible for the production of male steroid hormones, such as testosterone, and are important in male sexual differentiation.

DYSGENIC

Showing failed or disrupted morphology.

PARACRINE

A form of cell–cell communication that depends on a secreted substance that acts over a short distance and does not enter the circulation.

CANALIZE

Guided down a narrowly constrained pathway.

GUT MESENTERY

The tissue that is connected to the dorsal wall that supports the gut in the body cavity.

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Brennan, J., Capel, B. One tissue, two fates: molecular genetic events that underlie testis versus ovary development. Nat Rev Genet 5, 509–521 (2004). https://doi.org/10.1038/nrg1381

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