Reduced-folate carrier (RFC) is expressed in placenta and yolk sac, as well as in cells of the developing forebrain, hindbrain, neural tube, craniofacial region, eye, limb buds and heart.
BACKGROUND
Folate is essential for cellular proliferation and tissue regeneration. As mammalian cells cannot synthesize folates de novo, tightly regulated cellular uptake processes have evolved to sustain sufficient levels of intracellular tetrahydrofolate cofactors to support biosynthesis of purines, pyrimidines, and some amino acids (serine, methionine). Though reduced-folate carrier (RFC) is one of the major proteins mediating folate transport, knowledge of the developmental expression of RFC is lacking. We utilized in situ hybridization and immunolocalization to determine the developmental distribution of RFC message and protein, respectively.


RESULTS
In the mouse, RFC transcripts and protein are expressed in the E10.0 placenta and yolk sac. In the E9.0 to E11.5 mouse embryo RFC is widely detectable, with intense signal localized to cell populations in the neural tube, craniofacial region, limb buds and heart. During early development, RFC is expressed throughout the eye, but by E12.5, RFC protein becomes localized to the retinal pigment epithelium (RPE).


CONCLUSIONS
Clinical studies show a statistical decrease in the number of neural tube defects, craniofacial abnormalities, cardiovascular defects and limb abnormalities detected in offspring of female patients given supplementary folate during pregnancy. The mechanism, however, by which folate supplementation ameliorates the occurrence of developmental defects is unclear. The present work demonstrates that RFC is present in placenta and yolk sac and provides the first evidence that it is expressed in the neural tube, craniofacial region, limb buds and heart during organogenesis. These findings suggest that rapidly dividing cells in the developing neural tube, craniofacial region, limb buds and heart may be particularly susceptible to folate deficiency.
Maddox
Dennis M
DM
Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, USA. oxmandm@yahoo.com
Manlapat
Anna
A
Roon
Penny
P
Prasad
Puttur
P
Ganapathy
Vadivel
V
Smith
Sylvia B
SB
D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000276:immunology; D004622:Embryo, Mammalian / Q000737:chemistry*; D005123:Eye / Q000737:chemistry / Q000196:embryology; D005260:Female; D006321:Heart / Q000196:embryology; D007150:Immunohistochemistry; D018878:Limb Buds / Q000737:chemistry / Q000196:embryology; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D009432:Neural Crest / Q000737:chemistry / Q000196:embryology; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000737:chemistry / Q000196:embryology; D010920:Placenta / Q000737:chemistry / Q000196:embryology; D011247:Pregnancy; D016548:Prosencephalon / Q000737:chemistry / Q000196:embryology; D012333:RNA, Messenger / Q000096:biosynthesis; D058978:Reduced Folate Carrier Protein; D012249:Rhombencephalon / Q000737:chemistry / Q000196:embryology; D014599:Uterus / Q000737:chemistry; D015017:Yolk Sac / Q000737:chemistry / Q000196:embryology
D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D010455:Peptides; D012333:RNA, Messenger; D058978:Reduced Folate Carrier Protein; C548700:Slc19a1 protein, mouse