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:

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

Fetal macrophages mediate vascularization and cord formation during testis organogenesis

Authors
Capel, B; DeFalco, T; Cool, J
MLA Citation
Capel, Blanche, et al. “Fetal macrophages mediate vascularization and cord formation during testis organogenesis.” Faseb Journal, vol. 29, FEDERATION AMER SOC EXP BIOL, 2015.
URI
https://scholars.duke.edu/individual/pub1091041
Source
wos
Published In
Faseb Journal
Volume
29
Published Date

Differentiation of fetal sertoli cells in the adult testis.

Sertoli cells proliferate and construct seminiferous tubules during fetal life, then undergo differentiation and maturation in the prepubertal testes. In the adult testes, mature Sertoli cells maintain spermatogonia and support spermatogenesis during the entire lifetime. Although Sertoli-like cells have been derived from iPS cells, they tend to remain immature. To investigate whether Sertoli cells can spontaneously acquire the ability to support spermatogenesis when transferred into the adult testis, we transplanted mouse fetal testicular cells into a Sertoli-depleted adult testis. We found that donor E12.5, E14.5 and E16.5 Sertoli cells colonized adult seminiferous tubules and supported host spermatogenesis 2 months after transplantation, demonstrating that immature fetal Sertoli cells can undergo sufficient maturation in the adult testis to become functional. This technique will be useful to analyze the developmental process of Sertoli cell maturation and to investigate the potential of iPS-derived Sertoli cells to colonize, undergo maturation, and support spermatogenesis within the testis environment.
Authors
Yokonishi, T; Capel, B
MLA Citation
Yokonishi, Tetsuhiro, and Blanche Capel. “Differentiation of fetal sertoli cells in the adult testis.Reproduction (Cambridge, England), vol. 162, no. 2, July 2021, pp. 141–47. Epmc, doi:10.1530/rep-21-0106.
URI
https://scholars.duke.edu/individual/pub1484354
PMID
34085952
Source
epmc
Published In
Reproduction
Volume
162
Published Date
Start Page
141
End Page
147
DOI
10.1530/rep-21-0106