title: Use of a murine embryonic stem cell line that is sensitive to high glucose environment to model neural tube development in diabetic pregnancy.
abstract: BACKGROUND
  Neural tube defects (NTDs) are significantly increased by maternal diabetes. Embryonic stem cells (ESC) that can differentiate into neuroepithelium and can sense supraphysiological glucose concentrations would be very valuable to simulate the effects of maternal diabetes on molecular and cellular processes during neural tube formation.
  
  
  METHODS
  LG-ESC, a recently established ESC line that expresses the glucose transporter, Scl2a2, and is sensitive to elevated glucose concentrations, were grown for up to 8 days in a three-dimensional culture to form neural cysts. We tested whether high glucose media inhibits expression of Pax3, a gene that is required for neural tube closure and whose expression is inhibited in embryos of diabetic mice, and inhibits formation of neural cysts.
  
  
  RESULTS
  Pax3 expression was detected after 4 days of culture and increased with time. Pax3 expression was inhibited by high glucose media, but not if cells had been cultured in low glucose media for the first 4 days of culture. Pax7, which is also expressed in dorsal neural tube, was not detected. Pax6, which is expressed in the ventral neural tube, was detected only after 8 days of culture, but was not inhibited by high glucose. High glucose media did not inhibit formation of neural cysts.
  
  
  CONCLUSIONS
  LG-ESC can be used as a model of embryonic exposure to a diabetic environment during neural tube development. While high glucose exposure inhibits expression of a gene required for neural tube closure, it may not inhibit all of the processes involved in formation of a neural tube-like structure.
authors.affiliation: Section on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, Massachusetts.
authors.forename: Kaitlyn
authors.initials: K
authors.lastname: Sanders
authors.forename: Jin Hyuk
authors.initials: JH
authors.lastname: Jung
authors.forename: Mary R
authors.initials: MR
authors.lastname: Loeken
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D016640:Diabetes, Gestational / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D051273:Glucose Transporter Type 2 / Q000096:biosynthesis; D018398:Homeodomain Proteins / Q000378:metabolism; D006943:Hyperglycemia; D051379:Mice; D064231:Nestin / Q000378:metabolism; D054259:Neural Tube / Q000196:embryology*; D009436:Neural Tube Defects; D000072041:PAX3 Transcription Factor; D000071841:PAX6 Transcription Factor; D051763:PAX7 Transcription Factor / Q000378:metabolism; D051761:Paired Box Transcription Factors / Q000096:biosynthesis* / Q000378:metabolism; D011247:Pregnancy; D012097:Repressor Proteins / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D000199:Actins; D005136:Eye Proteins; D051273:Glucose Transporter Type 2; D018398:Homeodomain Proteins; C577485:Nes protein, mouse; D064231:Nestin; D000072041:PAX3 Transcription Factor; D000071841:PAX6 Transcription Factor; D051763:PAX7 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; C497322:Pax7 protein, mouse; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; C495682:Slc2a2 protein, mouse; C098693:Sox1 protein, mouse; D000509:alpha-Fetoproteins; C544013:alpha-smooth muscle actin, mouse; C068686:Pax3 protein, mouse; D005947:Glucose
keywords: Glut2; Pax3; Scl2a2; embryonic stem cells; hyperglycemia; neural tube defect; pregestational diabetic pregnancy