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Hum. Reprod. Advance Access published online on July 8, 2008
Human Reproduction, doi:10.1093/humrep/den262
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Distinct GAGE and MAGE-A expression during early human development indicate specific roles in lineage differentiation

Morten F. Gjerstorff1, Linda Harkness1,2, Moustapha Kassem1,2, Ulrik Frandsen1,2, Ole Nielsen3, Melissa Lutterodt4, Kjeld Møllgård5 and Henrik J. Ditzel1,6,7

1 Medical Biotechnology Center, University of Southern Denmark, Winsloewparken 25, DK-5000 Odense C, Denmark 2 Department of Endocrinology and Metabolism, Odense University Hospital, Sdr. Boulevard 29, DK-5000 Odense C, Denmark 3 Department of Clinical Pathology, Odense University Hospital, Winsloewparken 15, DK-5000 Odense C, Denmark 4 Laboratory for Reproductive Biology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Ø Copenhagen, Denmark 5 Department of Cellular and Molecular Medicine, the Panum Institute, University of Copenhagen, Blegdamsvej 3 DK-2100 Copenhagen, Denmark 6 Department of Oncology, Odense University Hospital, Sdr. Boulevard 29 DK-5000 Odense, Denmark

7 Correspondence address. Tel +45-65503781; Fax: +45-65503922; E-mail: hditzel@health.sdu.dk

BACKGROUND: Expression of cancer/testis-associated proteins (CTAs) has traditionally been considered to be restricted to germ cells in normal tissues and to different types of malignancies. We have evaluated the potential role of CTAs in early human development.

METHODS: Using immunohistochemistry and RT–PCR, we investigated the expression of CTAs in differentiated human embryonic stem cells (hESC) and in late embryos and early fetuses.

RESULTS: We found that melanoma antigen A (MAGE-A) family members were expressed during differentiation of hESC to embryoid bodies and in teratomas, and overlapped with expression of the neuroectodermal markers beta-tubulin 3, Pax6 and nestin. A widespread expression of MAGE-A was also observed in neurons of the early developing central nervous system and peripheral nerves. G antigen (GAGE) expression was present in the early ectoderm of embryos, including cells of the ectodermal ring and apical epidermal ridge. Neuroectodermal cells in the floor plate and adjacent processes and endfeet of radial glial cells also expressed GAGE. In addition, GAGE family members were expressed in the peripheral adrenal cortex of 6–9-week-old embryos and fetuses, which specifically correlated with massive cellular proliferation and establishment of the definitive and fetal zones. Overlapping expression of MAGE-A and GAGE proteins occurred in migrating primordial germ cells.

CONCLUSIONS: Our results show that CTAs, in addition to their role in germ cells, may be involved in early development of various types of somatic cells, and suggest that they are implicated in specific differentiation processes.

Key words: GAGE/MAGE-A/human development/hESC/teratoma

Submitted on April 8, 2008; resubmitted on May 16, 2008; accepted on May 28, 2008.


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