Late effects of retinoic acid on neural crest and aspects of rhombomere

E Gale, V Prince, A Lumsden, J Clarke, N Holder, M Maden

Research output: Contribution to journalArticlepeer-review

74 Citations (Scopus)

Abstract

We exposed st.10 chicks to retinoic acid (RA), both globally, and locally to individual rhombomeres, to look at its role in specification of various aspects of hindbrain derived morphology. Previous studies have looked at RA exposure at earlier stages, during axial specification. Stage 10 is the time of morphological segmentation of the hindbrain and is just prior to neural crest migration. Rhombomere 4 localised RA injections result in specific alterations of pathways some crest cells that normally migrate to sites of differentiation of neurogenic derivatives. The r4 crest cells that give rise to mesenchymal derivatives are unaffected. In addition, r4 gene expression is also partially altered by RA; within 6 hours of r4 exposure to RA, ectopic expression of Krox-20 is seen in r4 and Hoxb-1 expression is lost while Hoxa-2 expression continues normally. When we examined these RA-treated animals later in development, they showed an anterior displacement of the facial ganglion in addition to a mis-direction of the extensions of its distal axons and a dramatic decrease in the number of contralateral vestibuloacoustic neurons normally seen in r4. Only this r4-specific neuronal type is affected in r4; the motor neuron projections seem normal in experimental animals. The specificity of this result, combined with the loss of Hoxb-1 expression in r4 and the work by Krumlauf and co-workers showing gain of contralateral neurons co-localised with ectopic Hoxb-1 expression, indicates a role for Hoxb-1 and RA in the specification of this cell type in normal development. These results suggest that RA, at st.10, is able to affect some aspects of segment identity while leaving others unchanged.
Original languageEnglish
Pages (from-to)783-93
Number of pages11
JournalDevelopment (Cambridge): for advances in developmental biology and stem cells
Volume122
Issue number3
Publication statusPublished - Mar 1996

Keywords

  • Cell Movement
  • Rhombencephalon
  • Animals
  • Homeodomain Proteins
  • Chick Embryo
  • DNA-Binding Proteins
  • Neural Crest
  • Morphogenesis
  • RNA, Messenger
  • Phenotype
  • Genes, Homeobox
  • Base Sequence
  • Transcription Factors
  • DNA Primers
  • Molecular Sequence Data
  • Tretinoin
  • Early Growth Response Protein 2
  • Trans-Activators
  • Gene Expression Regulation, Developmental

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