Abstract
During spermatogenesis in the mammalian testis, stem cells (spermatogonia) differentiate into spermatocytes, which subsequently undergo two consecutive meiotic divisions to give rise to haploid spermatids. These cells are initially round but progressively elongate, condense their nuclei, acquire flagellar and acrosomal structures, and shed a significant amount of their cytoplasm to form spermatozoa (the sperm cells) in a developmental cascade termed spermiogenesis1,2. Defects in these processes will lead to a lack of mature sperm cells (azoospermia), which is a major cause of male infertility in the human population3. Here we report that a cell-surface protein of the immunoglobulin superfamily, junctional adhesion molecule-C (JAM-C), is critically required for the differentiation of round spermatids into spermatozoa in mice. We found that Jam-C is essential for the polarization of round spermatids, a function that we attribute to its role in the assembly of a cell polarity complex.
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Acknowledgements
We thank B. Margolis, T. Pawson, E. Peles, A. Suzuki, A. Le Bivic, C. Nobes and P. Parker for reagents and N. Hogg for comments on the manuscript. This work was funded by Cancer Research UK, the EMBO Young Investigator Program (R.H.A.), the Swiss National Science Foundation (M.A.L. and B.A.I.) and Oncosuisse (B.A.I).
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Supplementary information
Supplementary Figure 1
JAM-C gene targeting strategy and verification of the null allele. (PDF 146 kb)
Supplementary Figure 2
Histology showing the lack of mature spermatozoa in the epididymis of JAM-C-deficient mice. (PDF 176 kb)
Supplementary Figure 3
Data confirming the integrity of mutant Sertoli-Sertoli tight junctions. (PDF 214 kb)
Supplementary Figure 4
Additional immunofluorescence data for cell polarity proteins. (PDF 136 kb)
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Gliki, G., Ebnet, K., Aurrand-Lions, M. et al. Spermatid differentiation requires the assembly of a cell polarity complex downstream of junctional adhesion molecule-C. Nature 431, 320–324 (2004). https://doi.org/10.1038/nature02877
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DOI: https://doi.org/10.1038/nature02877
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