Methanol exposure interferes with morphological cell movements in the Drosophila embryo and causes increased apoptosis in the CNS.
Despite the significant contributions of tissue culture and bacterial models to toxicology, whole animal models for developmental neurotoxins are limited in availability and ease of experimentation. Because Drosophila is a well understood model for embryonic development that is highly accessible, we asked whether it could be used to study methanol developmental neurotoxicity. In the presence of 4% methanol, approximately 35% of embryos die and methanol exposure leads to severe CNS defects in about half those embryos, where the longitudinal connectives are dorsally displaced and commissure formation is severely reduced. In addition, a range of morphological defects in other germ layers is seen, and cell movement is adversely affected by methanol exposure. Although we did not find any evidence to suggest that methanol exposure affects the capacity of neuroblasts to divide or induces inappropriate apoptosis in these cells, in the CNS of germ band retracted embryos, the number of apoptotic nuclei is significantly increased in methanol-exposed embryos in comparison to controls, particularly in and adjacent to the ventral midline. Apoptosis contributes significantly to methanol neurotoxicity because embryos lacking the cell death genes grim, hid, and reaper have milder CNS defects resulting from methanol exposure than wild-type embryos. Our data suggest that when neurons and glia are severely adversely affected by methanol exposure, the damaged cells are cleared by apoptosis, leading to embryonic death. Thus, the Drosophila embryo may prove useful in identifying and unraveling mechanistic aspects of developmental neurotoxicity, specifically in relation to methanol toxicity.
Department of Pathology, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA. dervlam@umich.edu
Dervla M
DM
Mellerick
Heather
H
Liu
D000818:Animals; D017209:Apoptosis; D001973:Bromodeoxyuridine / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D002490:Central Nervous System / Q000166:cytology* / Q000196:embryology; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism; D004625:Embryo, Nonmammalian; D004628:Embryonic Structures / Q000187:drug effects / Q000378:metabolism; D017344:Genes, Insect / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D000432:Methanol / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*
D029721:Drosophila Proteins; D001973:Bromodeoxyuridine; D000432:Methanol