Retinoid signaling controls spermatogonial differentiation by regulating expression of replication-dependent core histone genes.
Journal: 2017/September - Development (Cambridge)
ISSN: 1477-9129
Abstract:
Retinoic acid (RA) signaling is crucial for spermatogonial differentiation, which is a key step for spermatogenesis. We explored the mechanisms underlying spermatogonial differentiation by targeting expression of a dominant-negative mutant of retinoic acid receptor α (RARα) specifically to the germ cells of transgenic mice to subvert the activity of endogenous receptors. Here we show that: (1) inhibition of retinoid signaling in germ cells completely blocked spermatogonial differentiation identical to vitamin A-deficient (VAD) mice; (2) the blockage of spermatogonial differentiation by impaired retinoid signaling resulted from an arrest of entry of the undifferentiated spermatogonia into S phase; and (3) retinoid signaling regulated spermatogonial differentiation through controlling expression of its direct target genes, including replication-dependent core histone genes. Taken together, our results demonstrate that the action of retinoid signaling on spermatogonial differentiation in vivo is direct through the spermatogonia itself, and provide the first evidence that this is mediated by regulation of expression of replication-dependent core histone genes.
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Development 143(9): 1502-1511

Retinoid signaling controls spermatogonial differentiation by regulating expression of replication-dependent core histone genes

State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
CAS-MPG Partner Institute for Computational Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA
Authors for correspondence (ude.usw@dlowsirgm; nc.ca.bcbis@nahgnim)
Received 2016 Jan 28; Accepted 2016 Mar 2.

ABSTRACT

Retinoic acid (RA) signaling is crucial for spermatogonial differentiation, which is a key step for spermatogenesis. We explored the mechanisms underlying spermatogonial differentiation by targeting expression of a dominant-negative mutant of retinoic acid receptor α (RARα) specifically to the germ cells of transgenic mice to subvert the activity of endogenous receptors. Here we show that: (1) inhibition of retinoid signaling in germ cells completely blocked spermatogonial differentiation identical to vitamin A-deficient (VAD) mice; (2) the blockage of spermatogonial differentiation by impaired retinoid signaling resulted from an arrest of entry of the undifferentiated spermatogonia into S phase; and (3) retinoid signaling regulated spermatogonial differentiation through controlling expression of its direct target genes, including replication-dependent core histone genes. Taken together, our results demonstrate that the action of retinoid signaling on spermatogonial differentiation in vivo is direct through the spermatogonia itself, and provide the first evidence that this is mediated by regulation of expression of replication-dependent core histone genes.

KEY WORDS: Spermatogonial differentiation, Spermatogenesis, Retinoic acid, Dominant-negative retinoic acid receptor, Testis, Replication-dependent core histone genes
ABSTRACT

Acknowledgements

We thank Dr G. Enders for providing anti-GCNA antibody and Dr C. Mendelsohn for providing dnRAR mice.

Acknowledgements

Footnotes

Competing interests

The authors declare no competing or financial interests.

Author contributions

Y.C. carried out most experiments and data analysis; L.M. and G.W. performed RNA sequencing data analysis; C.H., M.D.G. and M.-H.T. analyzed data and wrote the manuscript. All the authors were involved in the discussion on the manuscript.

Funding

This work supported by the National Natural Science Foundation of China [grant 31471401 to M.-H.T.] and the Ministry of Science and Technology of the People's Republic of China [grant 2014CB943101 to M.-H.T.] and National Institutes of Health [grants HD10808 to M.D.G. and HD06777 to M.-H.T. and M.D.G]. Deposited in PMC for release after 12 months.

Data availability

RNA sequencing data have been deposited at Gene Expression Omnibus with accession number {"type":"entrez-geo","attrs":{"text":"GSE79863","term_id":"79863"}}GSE79863.

Supplementary information

Supplementary information available online at http://dev.biologists.org/lookup/suppl/doi:10.1242/dev.135939/-/DC1

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