Cellular and Molecular Life Sciences

, Volume 72, Issue 8, pp 1559–1576 | Cite as

Retinoic acid signaling and neuronal differentiation

  • Amanda Janesick
  • Stephanie Cherie Wu
  • Bruce BlumbergEmail author


The identification of neurological symptoms caused by vitamin A deficiency pointed to a critical, early developmental role of vitamin A and its metabolite, retinoic acid (RA). The ability of RA to induce post-mitotic, neural phenotypes in various stem cells, in vitro, served as early evidence that RA is involved in the switch between proliferation and differentiation. In vivo studies have expanded this “opposing signal” model, and the number of primary neurons an embryo develops is now known to depend critically on the levels and spatial distribution of RA. The proneural and neurogenic transcription factors that control the exit of neural progenitors from the cell cycle and allow primary neurons to develop are partly elucidated, but the downstream effectors of RA receptor (RAR) signaling (many of which are putative cell cycle regulators) remain largely unidentified. The molecular mechanisms underlying RA-induced primary neurogenesis in anamniote embryos are starting to be revealed; however, these data have been not been extended to amniote embryos. There is growing evidence that bona fide RARs are found in some mollusks and other invertebrates, but little is known about their necessity or functions in neurogenesis. One normal function of RA is to regulate the cell cycle to halt proliferation, and loss of RA signaling is associated with dedifferentiation and the development of cancer. Identifying the genes and pathways that mediate cell cycle exit downstream of RA will be critical for our understanding of how to target tumor differentiation. Overall, elucidating the molecular details of RAR-regulated neurogenesis will be decisive for developing and understanding neural proliferation–differentiation switches throughout development.


Neurogenesis Retinoic acid receptor Proliferation-differentiation switch 



This study was supported by grants from the National Science Foundation (IOS-0719576, IOS-1147236) to B.B.


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Copyright information

© Springer Basel 2015

Authors and Affiliations

  • Amanda Janesick
    • 1
  • Stephanie Cherie Wu
    • 1
  • Bruce Blumberg
    • 1
    • 2
    Email author
  1. 1.Department of Developmental and Cell Biology, 2011 Biological Sciences 3University of CaliforniaIrvineUSA
  2. 2.Department of Pharmaceutical SciencesUniversity of CaliforniaIrvineUSA

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