Blanche Capel

Overview:

In mammals, the primary step in male sex determination is the initiation of testis development in the bipotential gonad primordium. This step depends on the Y-linked male sex-determining gene, Sry. Expression of Sry in the XY gonad, or as a transgene in an XX gonad, leads to the differentiation of Sertoli cells. Failures in Sertoli cell differentiation in the XY gonad result in sex reversal and ovary formation. In addition to Sertoli cell differentiation, we are studying the signaling pathways between Sry expression and early steps in testis organogenesis using mouse as a model system. Using genetic and cell biology approaches, we determined the origin of several key cell types of the testis. We also identified two pathways, proliferation and cell migration, that are controlled by Sry and lead to the architectural patterning of the testis. Currently we are investigating the novel hypothesis that reciprocal signals between the vasculature and Sertoli cells are involved in patterning testis cords. Testis organogenesis is an ideal model system to study the integration of vasculature during development of organ structure. In addition, we are investigating critical signals between Sertoli cells and germ cells during testis cord formation. Defects in these signals result in teratomas and gonadal blastomas, common neoplasias in young boys. Experimental approaches include the use of molecular and biochemical techniques, mutant mice, transgenics, organ culture assays, differential screens, immunocytochemistry imaging techniques, and classic mouse genetics.

Positions:

James B. Duke Distinguished Professor of Cell Biology

Cell Biology
School of Medicine

Professor of Cell Biology

Cell Biology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Affiliate of the Duke Regeneration Center

Regeneration Next Initiative
School of Medicine

Education:

Ph.D. 1989

University of Pennsylvania

Grants:

Identification of a Genetic Pathway Linking Temperature with Epigenetic Control of Gonad Determination in T. scripta

Administered By
Basic Science Departments
Awarded By
National Science Foundation
Role
Principal Investigator
Start Date
End Date

Defining Mechanisms of Ovarian Rescue

Administered By
Cell Biology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Opposing Pathways in Mammalian Sex Determination

Administered By
Cell Biology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Opposing Pathways in Mammalian Sex Determination

Administered By
Cell Biology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

DND1 Mediated Posttranscriptional Regulation in Murine Prospermatogonia During G1/G0 Arrest

Administered By
Cell Biology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

The PGD2 pathway, independently of FGF9, amplifies SOX9 activity in Sertoli cells during male sexual differentiation.

Activation by the Y-encoded testis determining factor SRY and maintenance of expression of the Sox9 gene encoding the central transcription factor of Sertoli cell differentiation are key events in the mammalian sexual differentiation program. In the mouse XY gonad, SOX9 upregulates Fgf9, which initiates a Sox9/Fgf9 feedforward loop, and Sox9 expression is stimulated by the prostaglandin D2 (PGD2) producing lipocalin prostaglandin D synthase (L-PGDS, or PTDGS) enzyme, which accelerates commitment to the male pathway. In an attempt to decipher the genetic relationships between Sox9 and the L-Pgds/PGD2 pathway during mouse testicular organogenesis, we found that ablation of Sox9 at the onset or during the time window of expression in embryonic Sertoli cells abolished L-Pgds transcription. By contrast, L-Pgds(-/-) XY embryonic gonads displayed a reduced level of Sox9 transcript and aberrant SOX9 protein subcellular localization. In this study, we demonstrated genetically that the L-Pgds/PGD2 pathway acts as a second amplification loop of Sox9 expression. Moreover, examination of Fgf9(-/-) and L-Pgds(-/-) XY embryonic gonads demonstrated that the two Sox9 gene activity amplifying pathways work independently. These data suggest that, once activated and maintained by SOX9, production of testicular L-PGDS leads to the accumulation of PGD2, which in turn activates Sox9 transcription and nuclear translocation of SOX9. This mechanism participates together with FGF9 as an amplification system of Sox9 gene expression and activity during mammalian testicular organogenesis.
Authors
Moniot, B; Declosmenil, F; Barrionuevo, F; Scherer, G; Aritake, K; Malki, S; Marzi, L; Cohen-Solal, A; Georg, I; Klattig, J; Englert, C; Kim, Y; Capel, B; Eguchi, N; Urade, Y; Boizet-Bonhoure, B; Poulat, F
MLA Citation
Moniot, Brigitte, et al. “The PGD2 pathway, independently of FGF9, amplifies SOX9 activity in Sertoli cells during male sexual differentiation.Development, vol. 136, no. 11, June 2009, pp. 1813–21. Pubmed, doi:10.1242/dev.032631.
URI
https://scholars.duke.edu/individual/pub868581
PMID
19429785
Source
pubmed
Published In
Development (Cambridge, England)
Volume
136
Published Date
Start Page
1813
End Page
1821
DOI
10.1242/dev.032631

Temporal differences in granulosa cell specification in the ovary reflect distinct follicle fates

Authors
Capel, B; Mork, L; Maatouk, DM; McMahon, JA; McMahon, AP; Zhang, P
MLA Citation
URI
https://scholars.duke.edu/individual/pub967833
Source
wos-lite
Published In
Human Reproduction
Volume
27
Published Date

Gonad Morphogenesis in Vertebrates: Somatic-Germ Cell Interactions.

Authors
MLA Citation
Capel, B. “Gonad Morphogenesis in Vertebrates: Somatic-Germ Cell Interactions.Annu Rev Cell Dev Biol, Jan. 2009. Pubmed, doi:10.1146/annurev.cellbio.042308.113350.
URI
https://scholars.duke.edu/individual/pub814770
PMID
19575664
Source
pubmed
Published In
Annu Rev Cell Dev Biol
Published Date
DOI
10.1146/annurev.cellbio.042308.113350

Temperature-dependent sex determination is mediated by pSTAT3 repression of Kdm6b

Authors
Weber, CJ; Zhou, Y; Lee, JG; Looger, L; Qian, G; Ge, G; Capel, B
MLA Citation
Weber, C. J., et al. “Temperature-dependent sex determination is mediated by pSTAT3 repression of Kdm6b.” Integrative and Comparative Biology, vol. 60, 2020, pp. E249–E249.
URI
https://scholars.duke.edu/individual/pub1447882
Source
wos-lite
Published In
Integrative and Comparative Biology
Volume
60
Published Date
Start Page
E249
End Page
E249

Patterning the Gonad in Four Dimensions.

Authors
Capel, B; Cool, J; Tang, H; Coveney, D; DeFalco, T
MLA Citation
Capel, Blanche, et al. “Patterning the Gonad in Four Dimensions.Biology of Reproduction, SOC STUDY REPRODUCTION, 2009, pp. 74–74.
URI
https://scholars.duke.edu/individual/pub868573
Source
wos
Published In
Biology of Reproduction
Published Date
Start Page
74
End Page
74