title: Retinoic acid regulates Kit translation during spermatogonial differentiation in the mouse.
abstract: In the testis, a subset of spermatogonia retains stem cell potential, while others differentiate to eventually become spermatozoa. This delicate balance must be maintained, as defects can result in testicular cancer or infertility. Currently, little is known about the gene products and signaling pathways directing these critical cell fate decisions. Retinoic acid (RA) is a requisite driver of spermatogonial differentiation and entry into meiosis, yet the mechanisms activated downstream are undefined. Here, we determined a requirement for RA in the expression of KIT, a receptor tyrosine kinase essential for spermatogonial differentiation. We found that RA signaling utilized the PI3K/AKT/mTOR signaling pathway to induce the efficient translation of mRNAs for Kit, which are present but not translated in undifferentiated spermatogonia. Our findings provide an important molecular link between a morphogen (RA) and the expression of KIT protein, which together direct the differentiation of spermatogonia throughout the male reproductive lifespan.
authors.affiliation: Department of Anatomy and Cell Biology, Brody School of Medicine, Greenville, NC, USA.
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Busada
authors.affiliation: Department of Anatomy and Cell Biology, Brody School of Medicine, Greenville, NC, USA.
authors.forename: Vesna A
authors.initials: VA
authors.lastname: Chappell
authors.affiliation: Department of Anatomy and Cell Biology, Brody School of Medicine, Greenville, NC, USA.
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Niedenberger
authors.affiliation: Department of Anatomy and Cell Biology, Brody School of Medicine, Greenville, NC, USA.
authors.forename: Evelyn P
authors.initials: EP
authors.lastname: Kaye
authors.affiliation: Department of Biochemistry and Molecular Biology, Brody School of Medicine, Greenville, NC, USA.
authors.forename: Brett D
authors.initials: BD
authors.lastname: Keiper
authors.affiliation: Department of Molecular Biosciences and the Center for Reproductive Biology, Washington State University, Pullman, WA, USA.
authors.forename: Cathryn A
authors.initials: CA
authors.lastname: Hogarth
authors.affiliation: Department of Anatomy and Cell Biology, Brody School of Medicine, Greenville, NC, USA; East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC, USA. Electronic address: geyerc@ecu.edu.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Geyer
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D015398:Signal Transduction; D013091:Spermatogenesis; D013093:Spermatogonia / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013737:Testis / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019869:Phosphatidylinositol 3-Kinases; D019009:Proto-Oncogene Proteins c-kit; D058570:TOR Serine-Threonine Kinases; D014212:Tretinoin; C102019:Stra8 protein, mouse
keywords: Kit; Retinoic acid; Spermatogenesis; Spermatogonia; Testis; Translation