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.

Hdl Handle:
http://hdl.handle.net/10675.2/98
Title:
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.
Authors:
Maddox, Dennis M; Manlapat, Anna K; Roon, Penny; Prasad, Puttur D; Ganapathy, Vadivel; Smith, Sylvia B
Abstract:
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.
Citation:
BMC Dev Biol. 2003 Jul 29; 3:6
Issue Date:
29-Oct-2003
URI:
http://hdl.handle.net/10675.2/98
DOI:
10.1186/1471-213X-3-6
PubMed ID:
12887734
PubMed Central ID:
PMC184426
Type:
Journal Article; Research Support, U.S. Gov't, P.H.S.
ISSN:
1471-213X
Appears in Collections:
Department of Cellular Biology and Anatomy: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorMaddox, Dennis Men_US
dc.contributor.authorManlapat, Anna Ken_US
dc.contributor.authorRoon, Pennyen_US
dc.contributor.authorPrasad, Puttur Den_US
dc.contributor.authorGanapathy, Vadivelen_US
dc.contributor.authorSmith, Sylvia Ben_US
dc.date.accessioned2010-09-24T22:03:18Z-
dc.date.available2010-09-24T22:03:18Z-
dc.date.issued2003-10-29en_US
dc.identifier.citationBMC Dev Biol. 2003 Jul 29; 3:6en_US
dc.identifier.issn1471-213Xen_US
dc.identifier.pmid12887734en_US
dc.identifier.doi10.1186/1471-213X-3-6en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/98-
dc.description.abstractBACKGROUND: 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.en_US
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.subject.meshAnimalsen_US
dc.subject.meshCarrier Proteins / biosynthesis / chemistry / immunologyen_US
dc.subject.meshEmbryo, Mammalian / chemistryen_US
dc.subject.meshEye / chemistry / embryologyen_US
dc.subject.meshFemaleen_US
dc.subject.meshHeart / embryologyen_US
dc.subject.meshImmunohistochemistryen_US
dc.subject.meshLimb Buds / chemistry / embryologyen_US
dc.subject.meshMaleen_US
dc.subject.meshMembrane Transport Proteinsen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred ICRen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshNeural Crest / chemistry / embryologyen_US
dc.subject.meshPeptides / immunology / metabolismen_US
dc.subject.meshPigment Epithelium of Eye / chemistry / embryologyen_US
dc.subject.meshPlacenta / chemistry / embryologyen_US
dc.subject.meshPregnancyen_US
dc.subject.meshProsencephalon / chemistry / embryologyen_US
dc.subject.meshRNA, Messenger / biosynthesisen_US
dc.subject.meshRhombencephalon / chemistry / embryologyen_US
dc.subject.meshUterus / chemistryen_US
dc.subject.meshYolk Sac / chemistry / embryologyen_US
dc.titleReduced-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.en_US
dc.typeJournal Articleen_US
dc.typeResearch Support, U.S. Gov't, P.H.S.en_US
dc.identifier.pmcidPMC184426en_US
dc.contributor.corporatenameDepartment of Cellular Biology and Anatomyen_US
dc.contributor.corporatenameDepartment of Obstetrics and Gynecologyen_US
dc.contributor.corporatenameDepartment of Biochemistry and Molecular Biologyen_US
dc.contributor.corporatenameDepartment of Ophthalmologyen_US
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