Arsenic-induced alterations in embryonic transcription factor gene expression: implications for abnormal neural development

Dev Genet. 1996;18(4):306-15. doi: 10.1002/(SICI)1520-6408(1996)18:4<306::AID-DVG4>3.0.CO;2-D.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arsenic / toxicity*
  • Blotting, Northern
  • Female
  • Gene Expression Regulation, Developmental / drug effects*
  • Maternal-Fetal Exchange
  • Mice
  • Mice, Inbred Strains
  • Neural Tube Defects / chemically induced
  • Neural Tube Defects / genetics*
  • Neural Tube Defects / pathology
  • Pregnancy
  • Transcription Factors / genetics*

Substances

  • Transcription Factors
  • Arsenic