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

TY - JOUR

T1 - Distinct GAGE and MAGE-A expression during early human development indicate specific roles in lineage differentiation

AU - Gjerstorff, Morten F

AU - Harkness, Linda

AU - Kassem, Moustapha

AU - Frandsen, Ulrik

AU - Lutterodt, Melissa

AU - Møllgård, Kjeld

AU - Ditzel, Henrik J

PY - 2008/10

Y1 - 2008/10

N2 - 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.

AB - 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.

KW - Adrenal Cortex/embryology

KW - Antigens, Neoplasm/metabolism

KW - Cell Differentiation

KW - Cell Lineage

KW - Cell Movement

KW - Central Nervous System/embryology

KW - Ectoderm/embryology

KW - Embryonic Development

KW - Embryonic Stem Cells/metabolism

KW - Female

KW - Fetal Development

KW - Fetus/metabolism

KW - Germ Cells/metabolism

KW - Humans

KW - Immunohistochemistry

KW - Male

KW - Melanoma-Specific Antigens

KW - Neoplasm Proteins/metabolism

KW - Neural Plate/embryology

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Teratoma/metabolism

U2 - 10.1093/humrep/den262

DO - 10.1093/humrep/den262

M3 - Journal article

C2 - 18611917

SN - 0268-1161

VL - 23

SP - 2194

EP - 2201

JO - Human Reproduction

JF - Human Reproduction

IS - 10

ER -