Effects of retinoic acid excess on expression of Hox-2.9 and Krox-20 and on morphological segmentation in the hindbrain of mouse embryos

EMBO J. 1991 Oct;10(10):2985-95.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics*
  • Early Growth Response Protein 2
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron, Scanning
  • Neural Crest / embryology
  • Neural Crest / growth & development
  • Nucleic Acid Hybridization
  • RNA Probes
  • Rhombencephalon / embryology*
  • Rhombencephalon / ultrastructure
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics*
  • Tretinoin*


  • DNA-Binding Proteins
  • Early Growth Response Protein 2
  • Egr2 protein, mouse
  • RNA Probes
  • Transcription Factors
  • Tretinoin