Dynamics of Notch Pathway Expression during Mouse Testis Post-Natal Development and along the Spermatogenic Cycle

Murta, Daniel; Batista, Marta; Silva, E.; Trindade, Alexandre; Henrique, Domingos; Duarte, António; Lopes-da-Costa, Luís

doi:10.1371/journal.pone.0072767

Cited by 53 publications

(67 citation statements)

References 55 publications

(94 reference statements)

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“…The role of Notch in the rodent testis remains controversial. Some reports suggest a possible role for Notch1 in the niche during spermatogenesis (Dirami et al, 2001;Hayashi et al, 2001;Murta et al, 2013), but functional studies could not demonstrate an essential function for Notch1 (Batista et al, 2012;Hasegawa et al, 2012). If N1IP::Cre HI is activated in germ cells during spermatogenesis, it will result in germline inheritance of an active reporter, manifest in uniform lacZ expression (stained blue by X-gal) in offspring of N1IP::Cre HI ; Rosa R26R/R26R fathers.…”

Section: Resultsmentioning

confidence: 99%

Second-generation Notch1 activity-trap mouse line (N1IP::CreHI) provides a more comprehensive map of cells experiencing Notch1 activity

et al. 2015

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Section: Resultsmentioning

confidence: 99%

Second-generation Notch1 activity-trap mouse line (N1IP::CreHI) provides a more comprehensive map of cells experiencing Notch1 activity

et al. 2015

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“…As a result, we hypothesize that JAGGED1 of Sertoli cells activates Notch signaling in germ cells. The testicular localization of Notch receptors in mouse testes has been reported in several studies [Dirami et al, 2001;Mori et al, 2003;von Schonfeldt et al, 2004;Hasegawa et al, 2012;Murta et al, 2013], but these reports are not consistent for NOTCH1/2 localization. In contrast, these reports were in accordance with NOTCH3 localization in spermatogonia [Dirami et al, 2001;Mori et al, 2003;Murta et al, 2013].…”

Section: Introductionmentioning

confidence: 84%

“…2 ). Previous investigations had reported that spermatogonia expressed NOTCH3 in mouse testes [Dirami et al, 2001;Mori et al, 2003;Murta et al, 2013], but the differentiation state of NOTCH3-expressing spermatogonia had not yet been analyzed. Our work is the first to reveal the differentiation state of NOTCH3-expressing spermatogonia.…”

Section: Discussionmentioning

confidence: 99%

“…Previous reports have shown that NOTCH1/2 are expressed in spermatogonia, spermatocytes, and spermatids [Mori et al, 2003;Murta et al, 2013], suggesting that the function of Notch3 is redundant in Notch3 mutant spermatogonia. The decreasing pattern of Hes1 expression during the development of testes suggested that Hes1 was expressed in spermatogonia.…”

Section: Notch3 In Mouse Spermatogoniamentioning

confidence: 96%

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Expression Profile of NOTCH3 in Mouse Spermatogonia

Okada

Fujimagari²,

Koya³

et al. 2017

Cells Tissues Organs

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Stable and sustainable spermatogenesis is supported by the strict regulation of self-renewal and differentiation of spermatogonial stem cells (SSC), which are a rare population of undifferentiated spermatogonia. It has been revealed that some signaling factors regulate the self-renewal of SSC; however, the molecular mechanism of SSC maintenance is still not completely understood. Notch signaling is an evolutionarily conserved juxtacrine signaling that plays important roles in the cell fate determination of various tissue stem cells. Recently, analyses of loss- and gain-of-function suggested that Notch signaling was necessary for normal spermatogenesis. However, the expression of Notch signal components in spermatogonia is still unclear. Here, we analyzed the distribution of NOTCH3-expressing spermatogonia and the target genes. Double immunostaining with differentiation markers revealed that NOTCH3 was expressed in some undifferentiated and differentiated spermatogonia in mouse testes. To define the target gene of Notch3 signaling in spermatogonia, we analyzed the mRNA expression pattern of Hes and Hey family genes during testis development. Hes1 abundance was decreased during testis development, suggesting that spermatogonia may express Hes1. Immunohistochemical analysis showed that HES1 was expressed in prepubertal spermatogonia, whereas it was expressed predominantly in adult Sertoli cells and weakly in adult spermatogonia. Furthermore, NOTCH3-HES1 double-positive spermatogonia were in pup and adult testes. These results suggest that Notch3 signaling in spermatogonia could promote Hes1 expression.

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“…Therefore, in general, Mvh and Oct4 are taken as the markers of germ stem cells. The NOTCH1 surface receptor is a key molecule in the Notch pathway; their expression can prompt the activity of the Notch pathway [34,35]. Hairy and enhancer of split 1 (Hes1) and hairy and enhancer of split 5 (Hes5) are the principal target genes of the Notch pathway, which regulate the proliferation and differentiation of cells [36,37].…”

Section: Discussionmentioning

confidence: 99%

The Expression of Markers Related to Ovarian Germline Stem Cells in the Mouse Ovarian Surface Epithelium and the Correlation with Notch Signaling Pathway

Pan

Sun

et al. 2015

Cell Physiol Biochem

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Background/Aims: Ovarian germline stem cells (OGSCs) have been shown to mainly exist in the ovarian surface epithelium (OSE), but the activity changes of germline stem cells during different reproductive stages and the potential regulatory signaling pathway are still unknown. The Notch signaling pathway plays a key role in cell development, primordial follicles and stem cell proliferation. However, whether it plays a role in the proliferation of OGSCs is unknown. Here, we analyzed the activity changes of germline stem cells and the correlation between germline stem cells and the Notch signaling pathway. Methods: The expression of germline stem cell markers Mvh, Ooc4 and the Notch molecules Notch1, Hes1, and Hes5 were detected during 3 days (3d), and 2, 12, 20 months (2m, 12m, 20m) mouse ovarian surface epithelium samples. DAPT, a specific inhibitor of the Notch pathway, was used to observe the influence of Notch signaling in the germline stem cells. Results: The results showed that the levels of MVH and OCT4 decreased substantially with reproductive age in ovarian surface epithelium, and the same tendency was detected in the Notch signaling molecules Notch1, Hes1 and Hes5. Dual-IF results showed that the germline stem cell markers were co-expressed with Notch molecules in the ovarian surface epithelium. While, the expression of MVH and OCT4 were reduced when the ovaries were treated with DAPT and the levels were attenuated with increasing dose of DAPT. Conclusion: Taken together, our results indicate that the viability of OGSCs decreased with the age of the mouse ovaries, and the activity of OGSCs in the ovarian surface epithelium may be related to the Notch signaling pathway.

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Dynamics of Notch Pathway Expression during Mouse Testis Post-Natal Development and along the Spermatogenic Cycle

Cited by 53 publications

References 55 publications

Second-generation Notch1 activity-trap mouse line (N1IP::CreHI) provides a more comprehensive map of cells experiencing Notch1 activity

Second-generation Notch1 activity-trap mouse line (N1IP::CreHI) provides a more comprehensive map of cells experiencing Notch1 activity

Expression Profile of NOTCH3 in Mouse Spermatogonia

The Expression of Markers Related to Ovarian Germline Stem Cells in the Mouse Ovarian Surface Epithelium and the Correlation with Notch Signaling Pathway

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