Distinct GAGE and MAGE-A expression during early human development indicate specific roles in lineage differentiation.
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.
Gjerstorff
Morten F
MF
Medical Biotechnology Center, University of Southern Denmark, Winsloewparken 25, DK-5000 Odense C, Denmark.
Harkness
Linda
L
Kassem
Moustapha
M
Frandsen
Ulrik
U
Nielsen
Ole
O
Lutterodt
Melissa
M
Møllgård
Kjeld
K
Ditzel
Henrik J
HJ
D000302:Adrenal Cortex / Q000196:embryology / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D002490:Central Nervous System / Q000196:embryology / Q000378:metabolism; D004475:Ectoderm / Q000196:embryology / Q000378:metabolism; D047108:Embryonic Development; D053595:Embryonic Stem Cells / Q000378:metabolism; D005260:Female; D047109:Fetal Development; D005333:Fetus / Q000378:metabolism; D005854:Germ Cells / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins / Q000378:metabolism / Q000502:physiology*; D054258:Neural Plate / Q000196:embryology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013724:Teratoma / Q000378:metabolism
D000951:Antigens, Neoplasm; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins