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 Chromatin State during Gonadal Sex Determination.

At embryonic day (E) 10.5, prior to gonadal sex determination, XX and XY gonads are bipotential and able to differentiate into either a testis or an ovary. At this point, they are transcriptionally and morphologically indistinguishable. Sex determination begins around E11.5 in the mouse when the supporting cell lineage commits to either Sertoli or granulosa cell fate. Testis-specific factors such as SRY and SOX9 drive differentiation of bipotential-supporting cells into the Sertoli cell pathway, whereas ovary-specific factors like WNT4 and FOXL2 guide differentiation into granulosa cells. It is known that these 2 pathways are mutually antagonistic, and repression of the alternative fate is critical for maintenance of the testis or ovary programs. While we understand much about the transcription factor networks guiding the process of sex determination, it is only more recently that we have begun to understand how this process is epigenetically controlled. Studies in the past decade have demonstrated the importance of the chromatin state for gene expression and cell fate commitment, with histone modifications and DNA accessibility having a direct role in gene regulation. It is now clear that the chromatin state during sex determination is dynamic and likely critical for the establishment and/or maintenance of the transcriptional programs. Prior to sex determination, supporting cells have similar chromatin structure and histone modification profiles, reflecting the bipotential nature of these cells. After differentiation to Sertoli or granulosa cells, the chromatin state acquires sex-specific profiles. The proteins that regulate the deposition of histone modifications or the opening of compact chromatin likely play an important role in Sertoli and granulosa cell fate commitment and gonad development. Here, we describe studies profiling the chromatin state during gonadal sex determination and one example in which depletion of Cbx2, a member of the Polycomb Repressive Complex 1 (PRC1), causes male-to-female sex reversal due to a failure to repress the ovarian pathway.
Authors
Dupont, S; Capel, B
MLA Citation
Dupont, Shannon, and Blanche Capel. “The Chromatin State during Gonadal Sex Determination.Sex Dev, vol. 15, no. 5–6, 2021, pp. 308–16. Pubmed, doi:10.1159/000520007.
URI
https://scholars.duke.edu/individual/pub1501318
PMID
34753132
Source
pubmed
Published In
Sex Dev
Volume
15
Published Date
Start Page
308
End Page
316
DOI
10.1159/000520007

Origin, specification and differentiation of a rare supporting-like lineage in the developing mouse gonad.

Gonadal sex determination represents a unique model for studying cell fate decisions. However, a complete understanding of the different cell lineages forming the developing testis and ovary remains elusive. Here, we investigated the origin, specification, and subsequent sex-specific differentiation of a previously uncharacterized population of supporting-like cells (SLCs) in the developing mouse gonads. The SLC lineage is closely related to the coelomic epithelium and specified as early as E10.5, making it the first somatic lineage to be specified in the bipotential gonad. SLC progenitors are localized within the genital ridge at the interface with the mesonephros and initially coexpress Wnt4 and Sox9. SLCs become sexually dimorphic around E12.5, progressively acquire a more Sertoli- or pregranulosa-like identity and contribute to the formation of the rete testis and rete ovarii. Last, we found that WNT4 is a crucial regulator of the SLC lineage and is required for normal development of the rete testis.
Authors
Mayère, C; Regard, V; Perea-Gomez, A; Bunce, C; Neirijnck, Y; Djari, C; Bellido-Carreras, N; Sararols, P; Reeves, R; Greenaway, S; Simon, M; Siggers, P; Condrea, D; Kühne, F; Gantar, I; Tang, F; Stévant, I; Batti, L; Ghyselinck, NB; Wilhelm, D; Greenfield, A; Capel, B; Chaboissier, M-C; Nef, S
MLA Citation
Mayère, Chloé, et al. “Origin, specification and differentiation of a rare supporting-like lineage in the developing mouse gonad.Sci Adv, vol. 8, no. 21, May 2022, p. eabm0972. Pubmed, doi:10.1126/sciadv.abm0972.
URI
https://scholars.duke.edu/individual/pub1521692
PMID
35613264
Source
pubmed
Published In
Science Advances
Volume
8
Published Date
Start Page
eabm0972
DOI
10.1126/sciadv.abm0972

Beatrice Mintz (1921-2022): an innovator in embryo research and cancer biology

Authors
MLA Citation
Capel, B. “Beatrice Mintz (1921-2022): an innovator in embryo research and cancer biology.” Development (Cambridge, England), vol. 149, no. 5, Mar. 2022. Scopus, doi:10.1242/dev.200607.
URI
https://scholars.duke.edu/individual/pub1512322
Source
scopus
Published In
Development
Volume
149
Published Date
DOI
10.1242/dev.200607

An interview with Dr Blanche Capel.

Authors
Kumar, TR
MLA Citation
Kumar, T. Rajendra. “An interview with Dr Blanche Capel.Biol Reprod, vol. 100, no. 4, Apr. 2019, pp. 865–68. Pubmed, doi:10.1093/biolre/ioz033.
URI
https://scholars.duke.edu/individual/pub1407008
PMID
30801633
Source
pubmed
Published In
Biol Reprod
Volume
100
Published Date
Start Page
865
End Page
868
DOI
10.1093/biolre/ioz033

A brief review of vertebrate sex evolution with a pledge for integrative research: towards 'sexomics'.

Triggers and biological processes controlling male or female gonadal differentiation vary in vertebrates, with sex determination (SD) governed by environmental factors or simple to complex genetic mechanisms that evolved repeatedly and independently in various groups. Here, we review sex evolution across major clades of vertebrates with information on SD, sexual development and reproductive modes. We offer an up-to-date review of divergence times, species diversity, genomic resources, genome size, occurrence and nature of polyploids, SD systems, sex chromosomes, SD genes, dosage compensation and sex-biased gene expression. Advances in sequencing technologies now enable us to study the evolution of SD at broader evolutionary scales, and we now hope to pursue a sexomics integrative research initiative across vertebrates. The vertebrate sexome comprises interdisciplinary and integrated information on sexual differentiation, development and reproduction at all biological levels, from genomes, transcriptomes and proteomes, to the organs involved in sexual and sex-specific processes, including gonads, secondary sex organs and those with transcriptional sex-bias. The sexome also includes ontogenetic and behavioural aspects of sexual differentiation, including malfunction and impairment of SD, sexual differentiation and fertility. Starting from data generated by high-throughput approaches, we encourage others to contribute expertise to building understanding of the sexomes of many key vertebrate species. This article is part of the theme issue 'Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part I)'.
Authors
Stöck, M; Kratochvíl, L; Kuhl, H; Rovatsos, M; Evans, BJ; Suh, A; Valenzuela, N; Veyrunes, F; Zhou, Q; Gamble, T; Capel, B; Schartl, M; Guiguen, Y
MLA Citation
Stöck, Matthias, et al. “A brief review of vertebrate sex evolution with a pledge for integrative research: towards 'sexomics'.Philos Trans R Soc Lond B Biol Sci, vol. 376, no. 1832, Aug. 2021, p. 20200426. Pubmed, doi:10.1098/rstb.2020.0426.
URI
https://scholars.duke.edu/individual/pub1488642
PMID
34247497
Source
pubmed
Published In
Philos Trans R Soc Lond B Biol Sci
Volume
376
Published Date
Start Page
20200426
DOI
10.1098/rstb.2020.0426