Disturbing endoderm signaling to anterior neural plate of vertebrates by the teratogen cadmium.
Cadmium accumulation in the mouse gut endoderm occurs until the closure of the vitelline duct (day 9 post-coitus; p.c.), producing anterior neural tube defects (NTD). The anterior part of the primitive endoderm, designated as the primary signaling center for anterior patterning, expresses several transcription factors of importance for head formation. Here, we studied the expression levels of some of these transcription factors (Hesx1, HNF3beta, Cerl, Otx2 and Sox2), and cell death induced after single cadmium administration to dams on days 7, 8 and 9 p.c. Stage specific down-regulation of Hesx1, Cerl, and Sox2, and an up-regulation of HNF3beta were observed. No effect was seen in Otx2 expression levels. Cell death was increased in the neuroepithelium of the cranial neural folds, and in areas where neural crest cells migrate, but not in the gut endoderm. It is proposed that cadmium-induced NTD is due to interference with head-inductive signals from the endoderm to the adjacent layers.
Fernandez
Estíbaliz L
EL
Department of Pharmaceutical Biosciences, Division of Toxicology, Biomedical Center, Uppsala University, Box 594, S-75124 Uppsala, Sweden.
Svenson
Camilla
C
Dencker
Lennart
L
Gustafson
Anne-Lee
AL
D000818:Animals; D019521:Body Patterning; D002104:Cadmium / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology*; D015536:Down-Regulation; D004707:Endoderm / Q000187:drug effects*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009436:Neural Tube Defects / Q000196:embryology; D015398:Signal Transduction / Q000187:drug effects; D013723:Teratogens / Q000633:toxicity*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D013723:Teratogens; D014157:Transcription Factors; D002104:Cadmium