Expression of Notch Pathway Components in Spermatogonia and Sertoli Cells of Neonatal Mice

Abstract

Members of the Notch gene family have been shown to play an important role in the control of cell fate in many developmental systems. We hypothesized that the fate of the male germ line stem cells may also be mediated through the Notch signaling pathway. We therefore sought to determine whether the components of the Notch pathway are expressed in the mouse testis. Western blot analysis revealed the expression of three Notch receptors (Notch 1, Notch 2, and Notch 3), Notch ligands (Jagged 1, Jagged 2, and Delta 1), and presenilin 1 (PS1) in neonatal mouse testis. We then examined their cellular localization by immunohistochemical analysis of cocultures of spermatogonia and Sertoli cells. The 3 Notch receptors were found to be expressed in spermatogonia. Sertoli cells expressed only Notch 2 receptor. Among the Notch ligands, Delta 1 and Jagged 1 were localized exclusively in spermatogonia and Sertoli cells, respectively. PS1 was apparent in both spermatogonia and Sertoli cells. The presence of Notch receptors and Notch ligands in spermatogonia and Sertoli cells indicates that these cells are capable of responding to and eliciting Notch signaling during the process of spermatogenesis. Key words: Cell fate, delta, jagged, presenilin, spermatogenesis.

Developmental Expression of p63 in the Mouse Testis

“…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]. Furthermore, increased expression of mRNAs of Notch 1 and Jagged 2 in developing rat testis coincides with the timimg of spermatocyte formation in the rat testis, and the localization of Notch 1 and Jagged 2 protein has been shown in the spermatocytes and spermatids by immunohistochemistry [7].…”

Mammalian gonocyte and spermatogonia differentiation: recent advances and remaining challenges

“…The NOTCH pathway has been shown to be involved in a multitude of processes, including cell proliferation, cell differentiation, and cell-cell communication. Furthermore, various components of the NOTCH pathway are expressed in neonatal and adult testes in both rodents and humans (Dirami et al 2001). Recent studies have demonstrated that NOTCH signaling in fetal Sertoli cells is critical for the maintenance of fetal gonocytes in a quiescent state and to exert a brake on the ability of fetal gonocytes to undergo differentiation .…”

NOTCH signaling in Sertoli cells regulates gonocyte fate

“…29 Through co-culture of 6-d-old BALB/c mouse Sertoli cells and germ cells and subsequent immunocytochemical analyses, Dirami et al demonstrated that 3 NOTCH receptors (NOTCH1, NOTCH2, and NOTCH3) and 2 NOTCH ligands (JAG1 and DLL1) were expressed on the cell surface of spermatogonia. 29 Sertoli cells were shown to express both ligands but only 1 of the 3 NOTCH receptors tested, NOTCH2.…”

“…29 Through co-culture of 6-d-old BALB/c mouse Sertoli cells and germ cells and subsequent immunocytochemical analyses, Dirami et al demonstrated that 3 NOTCH receptors (NOTCH1, NOTCH2, and NOTCH3) and 2 NOTCH ligands (JAG1 and DLL1) were expressed on the cell surface of spermatogonia. 29 Sertoli cells were shown to express both ligands but only 1 of the 3 NOTCH receptors tested, NOTCH2. 29 Concurrently, the studies of Hayashi et al demonstrated NOTCH1 and JAG2 immunostaining of rat and human spermatocytes as well as round and elongated spermatids in paraffin-embedded testes cross-sections.…”

“…29 Sertoli cells were shown to express both ligands but only 1 of the 3 NOTCH receptors tested, NOTCH2. 29 Concurrently, the studies of Hayashi et al demonstrated NOTCH1 and JAG2 immunostaining of rat and human spermatocytes as well as round and elongated spermatids in paraffin-embedded testes cross-sections. 30 Interestingly, the authors' examination of NOTCH1 and JAG2 testis expression in 11 patients with maturation arrest revealed a complete lack of NOTCH2 expression, despite continued expression of JAG2.…”