Gli family members are differentially expressed during the mitotic phase of spermatogenesis

Persengiev, Stephan P.; Kondova, Ivanela; Millette, Clarke F.; Kilpatrick, Daniel L.

doi:10.1038/sj.onc.1201068

Cited by 27 publications

(19 citation statements)

References 24 publications

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“…The testes, which mature when spermatogenesis is initiated, have high expression after male mice reach adulthood. These data fit well with previously published data for Gli activity in vivo (22)(23)(24).…”

Section: Resultssupporting

confidence: 82%

Gli Activity Correlates with Tumor Grade in Platelet-Derived Growth Factor–Induced Gliomas

et al. 2008

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Gli signaling is critical for central nervous system development and is implicated in tumorigenesis. To monitor Gli signaling in gliomas in vivo, we created platelet-derived growth factor-induced gliomas in a Gli-luciferase reporter mouse. We find that Gli activation is found in gliomas and correlates with grade. In addition, we find that sonic hedgehog (SHH) is expressed in these tumors and also correlates with grade. We identify microvascular proliferation and pseudopalisades, elements that define high-grade gliomas as SHH-producing microenvironments. We describe two populations of SHH-producing stromal cells that reside in perivascular niche (PVN), namely low-cycling astrocytes and endothelial cells. Using the Ptc-LacZ knock-in mouse as a second Gli responsive reporter, we show B-galactosidase activity in the PVN and in some tumors diffusely throughout the tumor. Lastly, we observe that SHH is similarly expressed in human gliomas and note that an intact tumor microenvironment or neurosphere conditions in vitro are required for Gli activity. [Cancer Res 2008;68(7):2241-9]

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Section: Resultssupporting

confidence: 82%

Gli Activity Correlates with Tumor Grade in Platelet-Derived Growth Factor–Induced Gliomas

et al. 2008

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“…7). The mRNA encoding Gli1 and Gli3 has previously only been detected in spermatogonia (Persengiev et al, 1997). However, our in situ hybridization data suggest they, together with Gli2, are also expressed in spermatocytes and round spermatids in the adult testis.…”

Section: Discussioncontrasting

confidence: 39%

“…Gli1 and Gli3 mRNAs have previously been detected in isolated mouse type A and B spermatogonia by Northern Blot analysis (Persengiev et al, 1997). Gli1 protein has been localized to the nuclei of germ cells, its detection beginning in pachytene spermatocytes and persisting through to round spermatids in the adult mouse testis.…”

Section: Introductionmentioning

confidence: 99%

Expression of hedgehog signalling components in adult mouse testis

Szczepny

Hime

Loveland

2006

Developmental Dynamics

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Hedgehog (Hh) signalling is known to regulate many aspects of normal development as well as being upregulated in various cancers. Signalling is mediated by the Gli family of zinc finger transcription factors. Based on observations that deletion of one of the three Hh genes, Dhh, leads to male infertility, we hypothesized that regulated expression of Hh signalling components would be a feature of adult spermatogenesis. We used in situ hybridization to characterise Gli gene expression in juvenile and adult mouse testes. In the first wave of spermatogenesis, mRNAs encoding all three Glis are detected in spermatogonia and Sertoli cells. In adult mouse testes, these transcripts are observed in spermatogonia and spermatocytes, with reduced signal intensity in round spermatids. The mRNAs encoding key effectors of Hh signalling, Ptc2, Smo, and Fu, are also most apparent in spermatogonia, spermatocytes, and to a lower extent in round spermatids. In contrast, mRNA encoding SuFu, a negative regulator of Hh signalling, was most predominant in round spermatids and the protein is evident in round and elongating spermatids, suggesting that SuFu protein may switch off Hh signalling in haploid germ cells. Overall, the coordinated expression pattern of these genes in adult mouse testis indicates a role for Hh signalling in spermatogenesis.

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“…In the absence of Shh signal, Gli1 and Gli2 are down-regulated in the nascent follicular keratinocytes, whose proliferative ability is thus impaired but can still differentiate (39,41). In another example, Desert hedgehog is required for the proliferation of testicular spermatogenic cells (41), in which Gli and basonuclin are also coexpressed (26,42,43). Therefore, our data here also suggest that basonuclin may be a target of the Hedgehog/Gli pathways in both of these developmental systems.…”

Section: Discussionmentioning

confidence: 50%

Gli Proteins Up-Regulate the Expression of Basonuclin in Basal Cell Carcinoma

Cui¹,

Elsam²,

Tian³

et al. 2004

Cancer Research

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Tumorigenesis is frequently accompanied by enhanced rRNA transcription, but the signaling mechanisms responsible for such enhancement remain unclear. Here, we report evidence suggesting a novel link between deregulated Hedgehog signaling and the augmented rRNA transcription in cancer. Aberrant activation of the Hedgehog pathway in keratinocytes is a hallmark of basal cell carcinoma (BCC), the most common cancer in light-skinned individuals. We show that Gli proteins, downstream effectors of the Hedgehog pathway, increase expression of a novel rRNA gene (rDNA) transcription factor, basonuclin, whose expression is markedly elevated in BCCs. The promoter of the human basonuclin gene contains a Gli-binding site, which is required for Gli protein binding and transcriptional activation. We show also that the level of 47S pre-rRNA is much higher in BCCs than in normal epidermis, suggesting an accelerated rRNA transcription in the neoplastic cells. Within BCC, those cells expressing the highest level of basonuclin also exhibit the greatest increase in 47S pre-rRNA, consistent with a role for basonuclin in increasing rRNA transcription in these cells. Our data suggest that Hedgehog-Gli pathway enhances rRNA transcription in BCC by increasing basonuclin gene expression.

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Gli family members are differentially expressed during the mitotic phase of spermatogenesis

Cited by 27 publications

References 24 publications

Gli Activity Correlates with Tumor Grade in Platelet-Derived Growth Factor–Induced Gliomas

Gli Activity Correlates with Tumor Grade in Platelet-Derived Growth Factor–Induced Gliomas

Expression of hedgehog signalling components in adult mouse testis

Gli Proteins Up-Regulate the Expression of Basonuclin in Basal Cell Carcinoma

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