Effects of retinoic acid excess on expression of Hox-2.9 and Krox-20 and on morphological segmentation in the hindbrain of mouse embryos.
Mouse embryos were exposed to maternally administered RA on day 8.0 or day 7 3/4 of development, i.e. at or just before the differentiation of the cranial neural plate, and before the start of segmentation. On day 9.0, the RA-treated embryos had a shorter preotic hindbrain than the controls and clear rhombomeric segmentation was absent. These morphological effects were correlated with alterations in the spatiotemporal distribution patterns of two genes, Hox-2.9 and Krox-20, which are expressed in the otic and preotic hindbrain and in specific neural crest cell populations. Hox-2.9 was expressed throughout the preotic hindbrain region, instead of being confined to rhombomere 4. Krox-20 was not expressed rostral to the Hox-2.9 domain, i.e. its normal rhombomere 3 domain was absent. The Hox-2.9/Krox-20 boundary was ill-defined, with patches of alternating expression of the two genes. In migrating neural crest cells, Hox-2.9 expression was both abnormally extensive and abnormally prolonged. Neural crest cells expressing Krox-20 remained close to the neural tube. Embryos exposed to RA on day 8 1/4 appeared to be morphologically normal. We suggest that early events leading to rhombomeric segmentation and rhombomere-specific gene expression are specifically vulnerable to raised RA levels, and may require RA levels lower than those in the region of somitic segmentation.
Department of Human Anatomy, Oxford, UK.
G M
GM
Morriss-Kay
P
P
Murphy
R E
RE
Hill
D R
DR
Davidson
D000818:Animals; D001345:Autoradiography; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D051767:Early Growth Response Protein 2; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D009432:Neural Crest / Q000196:embryology / Q000254:growth & development; D009693:Nucleic Acid Hybridization; D015347:RNA Probes; D012249:Rhombencephalon / Q000196:embryology* / Q000648:ultrastructure; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014212:Tretinoin
D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D015347:RNA Probes; D014157:Transcription Factors; D014212:Tretinoin