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Letters to Nature
Nature 340, 140 - 144 (13 July 1989); doi:10.1038/340140a0

Retinoic acid causes an anteroposterior transformation in the developing central nervous system

A. J. Durston, J. P. M. Timmermans, W. J. Hage, H. F. J. Hendriks*, N. J. de Vries, M. Heideveld & P. D. Nieuwkoop

Hubrecht Laboratory, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
* TNO Institute for Experimental Gerontology, Lange Kleiweg 151, 2280 HV Rijswijk, The Netherlands

ALL-trans retinoic acid (RA) is well known as a biologically active form of vitamin A and a teratogen1-8. The identification of nuclear receptors for this ligand9-11 suggests strongly that it is an endogenous signal molecule, and measurements of RA12 and teratogenic manipulations13-15 suggest further that RA is a mor-phogen specifying the anteroposterior axis during limb development. Besides the limb, RA and other retinoids affect development of other organs, including the central nervous system (CNS)4,6,7,16-18. None of these other effects has been investigated in detail. Our purpose here was to begin analysing the effects of RA on CNS development in Xenopus laevis. We find that RA acts on the developing CNS, transforming anterior neural tissue to a posterior neural specification. These and other19 findings raise the possibility that RA mediates an inductive interaction regulating anteroposterior differentiation within the CNS. Following recent reports implicating transforming growth factor-β2-like20,21 and fibroblast growth factor-like factors21,22 in mesoderm induction, this indicates that a different type of signal molecule (working through a nuclear receptor, not a plasma membrane receptor) might mediate inductive cell interactions during early embryonic development.

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