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:

Loss of Mafb and Maf distorts myeloid cell ratios and disrupts fetal mouse testis vascularization and organogenesis†.

Testis differentiation is initiated when Sry in pre-Sertoli cells directs the gonad toward a male-specific fate. Sertoli cells are essential for testis development, but cell types within the interstitial compartment, such as immune and endothelial cells, are also critical for organ formation. Our previous work implicated macrophages in fetal testis morphogenesis, but little is known about genes underlying immune cell development during organogenesis. Here, we examine the role of the immune-associated genes Mafb and Maf in mouse fetal gonad development, and we demonstrate that deletion of these genes leads to aberrant hematopoiesis manifested by supernumerary gonadal monocytes. Mafb; Maf double knockout embryos underwent initial gonadal sex determination normally, but exhibited testicular hypervascularization, testis cord formation defects, Leydig cell deficit, and a reduced number of germ cells. In general, Mafb and Maf alone were dispensable for gonad development; however, when both genes were deleted, we observed significant defects in testicular morphogenesis, indicating that Mafb and Maf work redundantly during testis differentiation. These results demonstrate previously unappreciated roles for Mafb and Maf in immune and vascular development and highlight the importance of interstitial cells in gonadal differentiation.
Authors
Li, S-Y; Gu, X; Heinrich, A; Hurley, EG; Capel, B; DeFalco, T
MLA Citation
Li, Shu-Yun, et al. “Loss of Mafb and Maf distorts myeloid cell ratios and disrupts fetal mouse testis vascularization and organogenesis†.Biol Reprod, vol. 105, no. 4, Oct. 2021, pp. 958–75. Pubmed, doi:10.1093/biolre/ioab098.
URI
https://scholars.duke.edu/individual/pub1482820
PMID
34007995
Source
pubmed
Published In
Biol Reprod
Volume
105
Published Date
Start Page
958
End Page
975
DOI
10.1093/biolre/ioab098

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

Sex Determination in Vertebrates Preface

Authors
MLA Citation
Capel, Blanche. “Sex Determination in Vertebrates Preface.” SEX DETERMINATION IN VERTEBRATES, edited by B. Capel, vol. 134, ELSEVIER ACADEMIC PRESS INC, 2019, pp. XIII–XVII.
URI
https://scholars.duke.edu/individual/pub1388505
Source
wos
Volume
134
Published Date
Start Page
XIII
End Page
XVII

Sex determination without sex chromosomes.

With or without sex chromosomes, sex determination is a synthesis of many molecular events that drives a community of cells towards a coordinated tissue fate. In this review, we will consider how a sex determination pathway can be engaged and stabilized without an inherited genetic determinant. In many reptilian species, no sex chromosomes have been identified, yet a conserved network of gene expression is initiated. Recent studies propose that epigenetic regulation mediates the effects of temperature on these genes through dynamic post-transcriptional, post-translational and metabolic pathways. It is likely that there is no singular regulator of sex determination, but rather an accumulation of molecular events that shift the scales towards one fate over another until a threshold is reached sufficient to maintain and stabilize one pathway and repress the alternative pathway. Investigations into the mechanism underlying sex determination without sex chromosomes should focus on cellular processes that are frequently activated by multiple stimuli or can synthesize multiple inputs and drive a coordinated response. 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
MLA Citation
Weber, Ceri, and Blanche Capel. “Sex determination without sex chromosomes.Philos Trans R Soc Lond B Biol Sci, vol. 376, no. 1832, Aug. 2021, p. 20200109. Pubmed, doi:10.1098/rstb.2020.0109.
URI
https://scholars.duke.edu/individual/pub1488643
PMID
34247500
Source
pubmed
Published In
Philos Trans R Soc Lond B Biol Sci
Volume
376
Published Date
Start Page
20200109
DOI
10.1098/rstb.2020.0109