GLI1 Localization in the Germinal Epithelial Cells Alternates Between Cytoplasm and Nucleus: Upregulation in Transgenic Mice Blocks Spermatogenesis in Pachytene

• Published in: Biology of reproduction Vol. 65; no. 6; pp. 1663 - 1671
• Main Authors: KROFT, Tim L, PATTERSON, John, JOON WON YOON, DOGLIO, Lynn, WALTERHOUSE, David O, IANNACCONE, Phillip M, GOLDBERG, Erwin
• Format: Journal Article
• Language: English
• Published: Madison, WI Society for the Study of Reproduction 01-12-2001
• Subjects: Animals; Apoptosis; Biological and medical sciences; Cell Nucleus - chemistry; Cytoplasm - chemistry; Epithelial Cells - chemistry; Epithelial Cells - ultrastructure; Gene Expression; Hedgehog Proteins; Isoenzymes - analysis; L-Lactate Dehydrogenase - analysis; Male; Mice; Mice, Knockout; Mice, Transgenic; Microtubules - chemistry; Mitosis; Oncogene Proteins - analysis; Oncogene Proteins - genetics; Sertoli Cells - ultrastructure; Spermatogenesis; Spermatozoa - enzymology; Testis - ultrastructure; Trans-Activators - genetics; Transcription Factors - analysis; Transcription Factors - genetics; Zinc Finger Protein GLI1; Zinc Fingers
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod65.6.1663

The zinc finger transcription factor GLI1 is the mediator of signaling by members of the Hedgehog (Hh) family. Male mice in
which Desert hedgehog (Dhh), an Hh homologue expressed in Sertoli cells of the testis, was knocked out are sterile, suggesting
that the Dhh/GLI1 pathway plays a role in spermatogenesis. Using an antiserum raised against human GLI1, we found that during
the first round of spermatogenesis, GLI1 expression is initially cytoplasmic, then shifts to the nuclei of Sertoli and germ
cells, and finally shifts back to the cytoplasm. In the adult mouse testis, GLI1 expression localized to the nuclei of germ
cells, beginning with pachytene cells and persisting through round spermatids. Localization of GLI1 in elongating spermatids
shifted from the nucleus to the cytoplasm and became associated with microtubules. We also examined a line of transgenic mice
that overexpressed human GLI1. Male mice in this line were sterile. Spermatogenesis was blocked at the pachytene stage, and
a subset of the morphologically indistinguishable pachytene cells underwent apoptosis. Patched-2, which is a Dhh receptor,
and Fused, another component of the signal transduction pathway, are expressed in Leydig cells and in primary and secondary
spermatocytes. Expression of GLI1 in the same cell types as Patched-2 and Fused and the disruption of spermatogenesis by GLI1
overexpression suggest that GLI1 is the mediator of the Dhh signal in the testis, and that it may be a regulator of spermatogenesis.