Undifferentiated spermatogonia regulateCyp26b1expression through NOTCH signaling and drive germ cell differentiation
Autor: | Reham Waheeb, Marvin L. Meistrich, Thomas X. Garcia, Gunapala Shetty, Marie Claude Hofmann, Pooja Gandhi, Parag Parekh, Vivek Jain |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Steroidogenic factor 1 endocrine system JAG1 Retinoic acid Notch signaling pathway SOX9 Biology Sertoli cell Biochemistry Cell biology 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure chemistry Genetics medicine Molecular Biology HEY1 030217 neurology & neurosurgery Germ cell Biotechnology |
Zdroj: | The FASEB Journal. 33:8423-8435 |
ISSN: | 1530-6860 0892-6638 |
Popis: | Cytochrome P450 family 26 subfamily B member 1 (CYP26B1) regulates the concentration of all-trans retinoic acid (RA) and plays a key role in germ cell differentiation by controlling local distribution of RA. The mechanisms regulating Cyp26b1 expression in postnatal Sertoli cells, the main components of the stem cell niche, are so far unknown. During gonad development, expression of Cyp26b1 is maintained by Steroidogenic Factor 1 (SF-1) and Sex-Determining Region Y Box-9 (SOX9), which ensure that RA is degraded and germ cell differentiation is blocked. Here, we show that the NOTCH target Hairy/Enhancer-of-Split Related with YRPW Motif 1 (HEY1), a transcriptional repressor, regulates germ cell differentiation via direct binding to the Cyp26b1 promoter and thus inhibits its expression in Sertoli cells. Further, using in vivo germ cell ablation, we demonstrate that undifferentiated type A spermatogonia are the cells that activate NOTCH signaling in Sertoli cells through their expression of the NOTCH ligand JAGGED-1 (JAG1) at stage VIII of the seminiferous epithelium cycle, therefore mediating germ cell differentiation by a ligand concentration-dependent process. These data therefore provide more insights into the mechanisms of germ cell differentiation after birth and potentially explain the spatiotemporal RA pulses driving the transition between undifferentiated to differentiating spermatogonia.-Parekh, P. A., Garcia, T. X., Waheeb, R., Jain, V., Gandhi, P., Meistrich, M. L., Shetty, G., Hofmann, M.-C. Undifferentiated spermatogonia regulate Cyp26b1 expression through NOTCH signaling and drive germ cell differentiation. |
Databáze: | OpenAIRE |
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