Sequential activation of Notch family receptors during mouse spermatogenesis

Abstract

The expression pattern of Notch family receptors during mouse spermatogenesis was examined by immunohistochemistry. The entire cytoplasm of spermatogonia, spermatocytes and spermatids showed staining with antibodies against extracellular domains of Notch1, 2 and 4. In contrast, the nuclei of spermatogonia showed staining with an antibody against the intracellular domain of Notch3, and the nuclei of spermatocytes and spermatids showed staining with antibodies against the intracellular domains of Notch1 and 4. During regeneration of spermatogonia in busulfan-treated mice, the nuclei of all proliferating cells showed staining for the intracellular domain of Notch3. Western blot analysis showed that the molecular weights of the intracellular domains of Notch1 and 3 localizing in the nuclear fraction were smaller than those in the cytoplasmic fraction. This was consistent with the theory that the intracellular domain of Notch was cleaved in the cytoplasm and translocated to the nucleus. These results suggest that different Notch signals are sequentially activated during mouse spermatogenesis and control the proliferation and differentiation of spermatogenic stem cells.

Developmental Expression of p63 in the Mouse Testis

“…Among these, TAp63 upregulates Jagged 1 and Jagged 2, while ∆Np63 downregulates Jagged 2 [26]. In the adult mouse testis, sequential activation of Notch signals has been suggested to regulate the proliferation and differentiation of spermatogenic cells [13]. In addition, expression of Notch 1, 2, 3, and their ligands Delta 1, Jagged 1, Jagged 2 in the testis, and the localization of Jagged 1 in Sertoli cells and Delta 1 in spermatogonia have been shown in the testis of 6-day-old mice [4].…”

NOTCH signaling in Sertoli cells regulates gonocyte fate

“…31 They also found nuclear-localized intracellular domain of NOTCH3 (NICD3) in spermatogonia and nuclearlocalized NICD1 and NICD4 in spermatocytes and spermatids, indicating that the respective receptors had been activated in these cells. 31 Additionally, Sahin et al demonstrated NOTCH2 immunostaining in spermatogonia and spermatocytes and NOTCH1 immunostaining in elongated spermatids. 32 Although the results of these studies generally disagree with regard to the particular receptor or ligand expressed in each cell type in the seminiferous epithelium, cumulatively, these studies strongly indicate that Sertoli cells and germ cells can elicit and respond to NOTCH signaling during spermatogenesis, and that the NOTCH signaling system may play a role in male germ cell differentiation and survival.…”

“…30 In 2003, Mori et al further characterized immunostaining of NOTCH1 to NOTCH4 in frozen sections of adult mouse testes and included the activated intracellular domains of the receptors in their analyses. 31 Their immunostaining demonstrated membrane-localized NOTCH1, NOTCH2, and NOTCH4 in spermatogonia, spermatocytes, and spermatids. 31 They also found nuclear-localized intracellular domain of NOTCH3 (NICD3) in spermatogonia and nuclearlocalized NICD1 and NICD4 in spermatocytes and spermatids, indicating that the respective receptors had been activated in these cells.…”

“…31 Their immunostaining demonstrated membrane-localized NOTCH1, NOTCH2, and NOTCH4 in spermatogonia, spermatocytes, and spermatids. 31 They also found nuclear-localized intracellular domain of NOTCH3 (NICD3) in spermatogonia and nuclearlocalized NICD1 and NICD4 in spermatocytes and spermatids, indicating that the respective receptors had been activated in these cells. 31 Additionally, Sahin et al demonstrated NOTCH2 immunostaining in spermatogonia and spermatocytes and NOTCH1 immunostaining in elongated spermatids.…”

Notch signaling as a therapeutic target in cancer: a new approach to the development of cell fate modifying agents

“…Thus, in the intestinal mucosa Notch signaling may have a classical 'lateral inhibition' function in the fate choice between the enterocyte lineage and the secretory lineage, and a prodifferentiation 'instructive' role in enterocyte development. Sequential Notch receptor activation has been suggested to occur during spermatogenesis (Mori et al, 2003) and in ovarian follicles (Johnson et al, 2001). There is strong evidence that Notch signaling participates in mammalian brain development, primarily inhibiting neuronal differentiation and allowing/ promoting glial differentiation (Morrison et al, 2000;Grandbarbe et al, 2003).…”