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First published online May 22, 2009
doi: 10.1242/10.1242/dev.020040

Development 136, 2091-2100 (2009)
Published by The Company of Biologists 2009
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Expression of retinoic acid receptor alpha in the germline is essential for proper cellular association and spermiogenesis during spermatogenesis

Sanny S. W. Chung1,2,3, Xiangyuan Wang1 and Debra J. Wolgemuth1,2,3,4,*

1 Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
2 Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, NY 10032, USA.
3 The Institute of Human Nutrition, Columbia University Medical Center, New York, NY 10032, USA.
4 The Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.

* Author for correspondence (e-mail: djw3{at}columbia.edu)

Accepted 14 April 2009

Signaling through vitamin A metabolites is indispensable for spermatogenesis, and disruption of retinoic acid receptor alpha (RAR{alpha}) function resulted in male sterility and aberrant spermatogenesis, which resembled vitamin A deficiency. Here we investigated the lineage- and cell-specific role of RAR{alpha}-mediated signaling during spermatogenesis using germ-cell transplantation and genetically manipulated mouse models. We demonstrated that RAR{alpha}-deficient germ-cell stem cells were able to repopulate germ-cell-depleted wild-type testes and initiate spermatogenesis; however, improper cellular associations and abnormal sperm formation were observed. We further generated RAR{alpha}-deficient mice that expressed RAR{alpha}-EGFP fusion protein uniquely in haploid germ cells. Strikingly, spermatid orientation, alignment and release, as well as sperm morphology, were normal and there was a partial rescue of sterility. These data provide the first direct evidence for a distinct requirement of RAR{alpha}-mediated retinoid signaling specifically in germ cells.

Key words: Retinoid signaling, Spermiogenesis, Germ-cell transplantation, Lineage-specific function, Mouse


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© The Company of Biologists Ltd 2009