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Constitutive activation of NOTCH1 signaling in Sertoli cells causes gonocyte exit from quiescence.

Publication ,  Journal Article
Garcia, TX; DeFalco, T; Capel, B; Hofmann, M-C
Published in: Dev Biol
May 1, 2013

Notch signaling components have long been detected in Sertoli and germ cells in the developing and mature testis. However, the role of this pathway in testis development and spermatogenesis remains unknown. Using reporter mice expressing green fluorescent protein following Notch receptor activation, we found that Notch signaling was active in Sertoli cells at various fetal, neonatal, and adult stages. Since Notch signaling specifies stem cell fate in many developing and mature organ systems, we hypothesized that maintenance and differentiation of gonocytes and/or spermatogonial stem cells would be modulated through this pathway in Sertoli cells. To this end, we generated mutant mice constitutively expressing the active, intracellular domain of NOTCH1 (NICD1) in Sertoli cells. We found that mutant Sertoli cells were morphologically normal before and after birth, but presented a number of functional changes that drastically affected gonocyte numbers and physiology. We observed aberrant exit of gonocytes from mitotic arrest, migration toward cord periphery, and premature differentiation before birth. These events, presumably unsupported by the cellular microenvironment, were followed by gonocyte apoptosis and near complete disappearance of the gonocytes by day 2 after birth. Molecular analysis demonstrated that these effects are correlated with a dysregulation of Sertoli-expressed genes that are required for germ cell maintenance, such as Cyp26b1 and Gdnf. Taken together, our results demonstrate that Notch signaling is active in Sertoli cells throughout development and that proper regulation of Notch signaling in Sertoli cells is required for the maintenance of gonocytes in an undifferentiated state during fetal development.

Duke Scholars

Published In

Dev Biol

DOI

EISSN

1095-564X

Publication Date

May 1, 2013

Volume

377

Issue

1

Start / End Page

188 / 201

Location

United States

Related Subject Headings

  • Spermatogonia
  • Signal Transduction
  • Sertoli Cells
  • Retinoic Acid 4-Hydroxylase
  • Receptor, Notch1
  • Phenotype
  • Organ Specificity
  • Mitosis
  • Mice
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Garcia, T. X., DeFalco, T., Capel, B., & Hofmann, M.-C. (2013). Constitutive activation of NOTCH1 signaling in Sertoli cells causes gonocyte exit from quiescence. Dev Biol, 377(1), 188–201. https://doi.org/10.1016/j.ydbio.2013.01.031
Garcia, Thomas Xavier, Tony DeFalco, Blanche Capel, and Marie-Claude Hofmann. “Constitutive activation of NOTCH1 signaling in Sertoli cells causes gonocyte exit from quiescence.Dev Biol 377, no. 1 (May 1, 2013): 188–201. https://doi.org/10.1016/j.ydbio.2013.01.031.
Garcia TX, DeFalco T, Capel B, Hofmann M-C. Constitutive activation of NOTCH1 signaling in Sertoli cells causes gonocyte exit from quiescence. Dev Biol. 2013 May 1;377(1):188–201.
Garcia, Thomas Xavier, et al. “Constitutive activation of NOTCH1 signaling in Sertoli cells causes gonocyte exit from quiescence.Dev Biol, vol. 377, no. 1, May 2013, pp. 188–201. Pubmed, doi:10.1016/j.ydbio.2013.01.031.
Garcia TX, DeFalco T, Capel B, Hofmann M-C. Constitutive activation of NOTCH1 signaling in Sertoli cells causes gonocyte exit from quiescence. Dev Biol. 2013 May 1;377(1):188–201.
Journal cover image

Published In

Dev Biol

DOI

EISSN

1095-564X

Publication Date

May 1, 2013

Volume

377

Issue

1

Start / End Page

188 / 201

Location

United States

Related Subject Headings

  • Spermatogonia
  • Signal Transduction
  • Sertoli Cells
  • Retinoic Acid 4-Hydroxylase
  • Receptor, Notch1
  • Phenotype
  • Organ Specificity
  • Mitosis
  • Mice
  • Male