Arsenic-induced alterations in embryonic transcription factor gene expression: implications for abnormal neural development.
We examined the morphological and molecular consequences of acute in utero exposure to teratogenic concentrations of arsenate. The treatment produced a dose-related increase in neural tube defects, along with a significant alteration in the pattern of gene expression for several transcription factors (creb, Hox 3.1, Pax3, and Emx-1) that were examined using in situ transcription and antisense RNA amplification procedures. On gestational day 9:0, there was a significant delay in the embryos progression through neural tube closure, accompanied by a significant downregulation of Hox 3.1 expression and a significant upregulation of Pax3, Emx-1, and creb. As both Hox 3.1 and Pax3 serve to regulate N-CAM expression, it is possible that abnormalities associated with N-CAM may compromise neural crest cell migration and normal neural tube closure.
Wlodraczyk
B
B
Department of Veterinary Anatomy and Public Health, Texas A & M University, College Station 77843-4458, USA.
Bennett
G D
GD
Calvin
J A
JA
Craig
J C
JC
Finnell
R H
RH
D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D015152:Blotting, Northern; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D008431:Maternal-Fetal Exchange; D051379:Mice; D008815:Mice, Inbred Strains; D009436:Neural Tube Defects / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D014157:Transcription Factors / Q000235:genetics*
D014157:Transcription Factors; D001151:Arsenic