Expression of hedgehog signalling components in adult mouse testis

Abstract

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.

Transcriptome profiling of the developing postnatal mouse testis using next-generation sequencing

“…Dhh, Shh, and Ihh are expressed at E11.5, and Dhh expression peaks at 6 dpn, while Shh and Ihh are expressed at relatively low levels at all stages of testicular development [74]. Our results are consistent with these findings, indicating that Dhh plays a more important role than Shh and Ihh in the Hh signaling pathway of mouse testicular development ( Figure S7).…”

“…The three Glis are observed in spermatogonia and Sertoli cells in the first wave of spermatogenesis, and can be detected in spermatogonia and spermatocytes in adult mice, while Ptch2 and Smo are also apparent in spermatogonia and spermatocytes; in contrast, Sufu is predominant in round spermatids [74]. Our results show that the expression levels of Gli1, Ptch1, Ptch2, and Smo decrease in PN2, whereas Sufu is transcriptionally activated.…”

“…There are three Hh genes in mammals: Sonic hedgehog (Shh), Desert hedgehog (Dhh), and Indian hedgehog (Ihh) [74]. Patched (PTCH) and Smoothened (SMO) are the main receptors of Hh proteins.…”

Transcriptome analysis of differentiating spermatogonia stimulated with kit ligand

“…In the testis is expressed at the beginning of the meiotic phase (Arama et al, 1998;Letwin et al, 1992 (Shao et al, 2001) Spermatogonial markers 1428639_at 0.58 Lin9 Required for the expression of the spermatogonial marker B-Myb (Latham et al, 1996;Pilkinton et al, 2007) 1422655_at 0.57 Ptch2 Patched homolog 2. A receptor for sonic hedgehog, expressed in spermatogonia, and at lower levels in spermatocytes (Szczepny et al, 2006) [no specific references are given for these genes, since description of their metabolic function can be found in the free databases at the link http://www.informatics.jax.org]. The KL-mediated down-regulation of the expression of several metabolic genes in spermatogonia is an.…”

Interacciones Epitelio-Mesenquimáticas en el Desarrollo Testicular

“…Existe evidencia que embriones que no expresan DHH en las células sustentaculares presentan una población reducida de células intersticiales fetales, con la consecuente producción insuficiente de andrógenos, ocasionando en el descenso testicular, atrofia genital y desarrollo de genitalia externa ambigua (Bitgood et al, 1996;Clark et al, 2000;Pierucci-Alves et al). Tras la unión al receptor PTCH1 en las células intersticiales fetales, DHH induce respuestas intracelulares por medio de factores de transcripción GLI1 y GLI2 (Szczepny et al, 2006;Sahin et al, 2014). Posteriormente, tanto DHH y PDGFA se ven implicadas en el desarrollo de las células intersticiales adultas (Bitgood et al; Chen & Liu).…”