title: Novel Mode of Defective Neural Tube Closure in the Non-Obese Diabetic (NOD) Mouse Strain.
abstract: Failure to close the neural tube results in birth defects, with severity ranging from spina bifida to lethal anencephaly. Few genetic risk factors for neural tube defects are known in humans, highlighting the critical role of environmental risk factors, such as maternal diabetes. Yet, it is not well understood how altered maternal metabolism interferes with embryonic development, and with neurulation in particular. We present evidence from two independent mouse models of diabetic pregnancy that identifies impaired migration of nascent mesodermal cells in the primitive streak as the morphogenetic basis underlying the pathogenesis of neural tube defects. We conclude that perturbed gastrulation not only explains the neurulation defects, but also provides a unifying etiology for the broad spectrum of congenital malformations in diabetic pregnancies.
authors.affiliation: Pennington Biomedical Research Center, Department of Regulation of Gene Expression, 6400 Perkins Road, Baton Rouge, LA 70808, USA.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Salbaum
authors.affiliation: Pennington Biomedical Research Center Department of Developmental Biology, 6400 Perkins Road, Baton Rouge, LA 70808, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Kruger
authors.affiliation: Pennington Biomedical Research Center, Department of Regulation of Gene Expression, 6400 Perkins Road, Baton Rouge, LA 70808, USA.
authors.forename: Jacalyn
authors.initials: J
authors.lastname: MacGowan
authors.affiliation: Pennington Biomedical Research Center Department of Developmental Biology, 6400 Perkins Road, Baton Rouge, LA 70808, USA.
authors.forename: Nils J
authors.initials: NJ
authors.lastname: Herion
authors.affiliation: Pennington Biomedical Research Center Cell Biology and Bioimaging Core Facility, 6400 Perkins Road, Baton Rouge, LA 70808, USA.
authors.forename: David
authors.initials: D
authors.lastname: Burk
authors.affiliation: Pennington Biomedical Research Center Department of Developmental Biology, 6400 Perkins Road, Baton Rouge, LA 70808, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Kappen
mesh_terms: D000818:Animals; D016640:Diabetes, Gestational / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005260:Female; D054262:Gastrulation / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D061346:Laser Capture Microdissection; D051379:Mice; D016688:Mice, Inbred NOD; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D054258:Neural Plate / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D009436:Neural Tube Defects / Q000196:embryology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy
chemical_list: D009419:Nerve Tissue Proteins