Identification of regulatory elements required for Stra8 expression in fetal ovarian germ cells of the mouse
| Autor: | Josephine Bowles, Chun-Wei Feng, Peter Koopman, Guillaume Burnet, Cassy M. Spiller, Kallayanee Chawengsaksophak, Fiona Ka Man Cheung |
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| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
Mutant Retinoic acid Ovary Biology Green fluorescent protein Cell biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine.anatomical_structure chemistry In vivo medicine Molecular Biology Gene Transcription factor 030217 neurology & neurosurgery Germ cell 030304 developmental biology Developmental Biology |
| Zdroj: | Development. 148 |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.194977 |
| Popis: | In mice, the entry of germ cells into meiosis crucially depends on the expression of stimulated by retinoic acid gene 8 (Stra8). Stra8 is expressed specifically in pre-meiotic germ cells of females and males, at fetal and postnatal stages, respectively, but the mechanistic details of its spatiotemporal regulation are yet to be defined. In particular, there has been considerable debate regarding whether retinoic acid is required, in vivo, to initiate Stra8 expression in the mouse fetal ovary. We show that the distinctive anterior-to-posterior pattern of Stra8 initiation, characteristic of germ cells in the fetal ovary, is faithfully recapitulated when 2.9 kb of the Stra8 promoter is used to drive eGFP expression. Using in vitro transfection assays of cutdown and mutant constructs, we identified two functional retinoic acid responsive elements (RAREs) within this 2.9 kb regulatory element. We also show that the transcription factor DMRT1 enhances Stra8 expression, but only in the presence of RA and the most proximal RARE. Finally, we used CRISPR/Cas9-mediated targeted mutation studies to demonstrate that both RAREs are required for optimal Stra8 expression levels in vivo. |
| Databáze: | OpenAIRE |
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