title: Retinoic acid influences the development of the inferior olivary nucleus in the rodent.
abstract: All-trans retinoic acid (atRA) is an endogenous morphogen that regulates gene transcription. Maternal 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.
authors.affiliation: Inst. Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujinuma
authors.forename: Shinji
authors.initials: S
authors.lastname: Hirano
authors.forename: Yoshika
authors.initials: Y
authors.lastname: Hayakawa
authors.forename: Margaret
authors.initials: M
authors.lastname: Clagett-Dame
authors.forename: Jinghua
authors.initials: J
authors.lastname: Zhang
authors.forename: Peter
authors.initials: P
authors.lastname: McCaffery
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D008953:Models, Anatomic; D009847:Olivary Nucleus / Q000196:embryology* / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014158:Transcription, Genetic; D014212:Tretinoin / Q000378:metabolism*; D014801:Vitamin A / Q000378:metabolism; D014802:Vitamin A Deficiency / Q000378:metabolism
chemical_list: D014801:Vitamin A; D014212:Tretinoin; D012313:RNA