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All‐ trans retinoic acid stimulates and maintains neurite outgrowth in nerve growth factor‐supported developing chick embryonic sympathetic neurons
Author(s) -
Plum L.A.,
ClagettDame M.
Publication year - 1996
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/(sici)1097-0177(199601)205:1<52::aid-aja5>3.0.co;2-4
Subject(s) - neurite , retinoic acid , biology , nerve growth factor , embryonic stem cell , retinoid x receptor , endocrinology , medicine , embryogenesis , microbiology and biotechnology , retinoid , neuron , embryo , receptor , transcription factor , neuroscience , cell culture , nuclear receptor , biochemistry , genetics , gene , in vitro
In explanted embryonic chick sympathetic neurons, all‐ trans retinoic acid (RA) aswell as nerve growth factor (NGF) were found to be required for neuronal survival and neuriteoutgrowth at early stages of development (day 6.5–7) in agreement with previous work(Rodriguez‐Tébar and Rohrer [1991] Development 112:813–820). The dependenceof neurons on all‐ trans RA for survival diminished at later stages of development.However, all‐ trans RA was found to be needed at all stages of development in order tomaximize neurite outgrowth. Further, removal of all‐ trans RA from the cultures led to arapid degeneration of the formed neurites, demonstrating the essentiality of all‐ trans RAfor both the development of neurites, and for the maintenance of existing neurites in culturedembryonic sympathetic neurons. The mechanism whereby all‐ trans RA exerts its effectson embryonic sympathetic neurons may involve activation of the nuclear retinoic acid andretinoid‐X receptor (RAR and RXR) families. The results of Northern blot analyses and/or reversetranscriptase‐polymerase chain reaction (RT‐PCR) studies show that embryonic sympatheticganglia express RARβ, RARγ and RXRγ mRNAs. RXRγ mRNA is expressedat highest levels in immature neurons that are not yet responsive to NGF (day 6.5–7) andmessage levels decline with increasing developmental age. In contrast, RARβ transcript levelsare barely detectable at day 6.5–7, and increase ∼4‐fold in ganglia from embryos atday 8.5–9 and decline thereafter. RT‐PCR studies show that RARγ mRNA isexpressed both early (day 6.5–7) and late (day 15) in ganglionic development. Transcriptsfor the NGF receptors, p75 NGFR and p140 trk were alsoexamined. The appearance of a single 2.7 kb p140 trk transcript coincideswith the time when RARβ mRNA is maximally expressed, raising the possibility that NGFreceptors may be targets of retinoid action. Evidence is also presented that all‐ trans RAmay enhance neurite outgrowth by mechanisms other than simply inducing NGF‐responsivenessof neurons. © 1996 Wiley‐Liss, Inc.