Abstract
During testis development, fetal Leydig cells increase their population from a pool of progenitor cells rather than from proliferation of a differentiated cell population. However, the mechanism that regulates Leydig stem cell self-renewal and differentiation is unknown. Here, we show that blocking Notch signaling, by inhibiting γ-secretase activity or deleting the downstream target gene Hairy/Enhancer-of-split 1, results in an increase in Leydig cells in the testis. By contrast, constitutively active Notch signaling in gonadal somatic progenitor cells causes a dramatic Leydig cell loss, associated with an increase in undifferentiated mesenchymal cells. These results indicate that active Notch signaling restricts fetal Leydig cell differentiation by promoting a progenitor cell fate. Germ cell loss and abnormal testis cord formation were observed in both gain- and loss-offunction gonads, suggesting that regulation of the Leydig/interstitial cell population is important for male germ cell survival and testis cord formation.
Original language | English (US) |
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Pages (from-to) | 3745-3753 |
Number of pages | 9 |
Journal | Development |
Volume | 135 |
Issue number | 22 |
DOIs | |
State | Published - 2008 |
Keywords
- Germ cell
- Hes1
- Leydig cell
- Mouse
- Notch
- Stem cells
- Testis cord
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology