Retinoic acid influences the development of the inferior olivary nucleus in the rodent

Miyuki Yamamoto, Masahiro Fujinuma, Shinji Hirano, Yoshika Hayakawa, Margaret Clagett-Dame, Jinghua Zhang, Peter John Andrew McCaffery

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


All-trans retinoic acid (atRA) is an endogenous morphogen that regulates gene transcription. Matemal exposure to atRA results in severe developmental abnormalities by disrupting normal patterns of atRA distribution. Previously, we have shown that the pontine nucleus, which originates from the rhombic lip, is severely atrophied in the mouse on exposure to atRA at gestational days 9 and 10. In this study, we show that this same period of atRA exposure has the contrary effect on the inferior olive and this rhombic lip derivative is expanded in volume and probably contains an increased number of cells. The posterior region of the inferior olive maintains a relatively normal shape but is significantly expanded in size. In contrast, the organization of the anterior inferior olive is severely disrupted. Because endogenous atRA levels are known to be higher in the region of the posterior inferior olive at the time of birth of inferior olivary neurons, these results suggest that endogenous atRA may promote the generation, or select the fate, of posterior neurons of the inferior olive. In support of this concept, a reduction in atRA resulting from vitamin A deficiency results in loss of cells of the posterior inferior olive. (c) 2005 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)421-433
Number of pages13
JournalDevelopmental Biology
Issue number2
Publication statusPublished - 15 Apr 2005


  • animals
  • brain
  • mammalian embryo
  • gene expression regulation, developmental
  • In situ hybridization
  • mice
  • mice, inbred C57BL
  • anatomic models
  • olivary nucleus
  • RNA
  • rats
  • time factors
  • genetic transcription
  • tretinoin
  • vitamin A
  • vitamin A deficiency
  • hindbrain
  • teratogenesis
  • hyperplasia
  • facial nucleus
  • migration
  • central nervous system
  • cerebellar development
  • fetal alcohol syndrome
  • binding proteins


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