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Hedgehog signaling pathway regulates gene expression profile of epididymal principal cells through the primary cilium
Author(s) -
Girardet Laura,
Bernet Agathe,
Calvo Ezéquiel,
Soulet Denis,
Joly-Beauparlant Charles,
Droit Arnaud,
Cyr Daniel G.,
Belleannée Clémence
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202000328r
Subject(s) - cilium , hedgehog , cyclopamine , microbiology and biotechnology , hedgehog signaling pathway , biology , signal transduction , extracellular , intraflagellar transport , gli2 , gli1 , epididymis , immune system , notch signaling pathway , gene , immunology , genetics , flagellum , sperm
Primary cilia (PC) are organelles that sense and respond to dynamic changes of the extracellular milieu through the regulation of target genes. By using the epididymis as a model system, we determined the contribution of primary cilia in the regulation of epithelial cell functions through the transduction of the Hedgehog (Hh) signaling pathway. Both Sonic (SHH) and Indian Hedgehog (IHH) ligands were detected in epididymal epithelial cells by confocal microscopy and found secreted in the extracellular space. Gene expression profiling preformed on ciliated epithelial cells indicated that 153 and 1052 genes were differentially expressed following treatment with the Hh agonist SAG or the Hh antagonist cyclopamine (Cyclo), respectively. Strikingly, gene ontology analysis indicated that genes associated with immune response were the most affected following Hh modulation. The contribution of epididymal PC to canonical Hh pathway transduction was validated by ciliobrevin D treatment, which induced a significant decrease in PC length and a reduction in the expression Hh signaling targets. Such findings bring us closer to a molecular understanding of the subtle immune balance observed in some epithelia, including the epididymis and the intestine, which are organs featuring both tolerance toward autoimmune spermatozoa (or commensal bacteria) and defense against pathogens.