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retinoic acid modifies.full

retinoic acid modifies.full - Development 112 945-958(1991...

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Development 112, 945-958 (1991) Printed in Great Britain © The Company of Biologists Limited 1991 945 Retinoic acid modifies the pattern of cell differentiation in the central nervous system of neurula stage Xenopus embryos A. RUIZ i ALTABA and T. M. JESSELL Howard Hughes Medical Institute, Center for Neurobiology and Behavior, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA Summary Neural cell markers have been used to examine the effect of retinoic acid (RA) on the development of the central nervous system (CNS) of Xenopus embryos. RA treat- ment of neurula stage embryos resulted in a concen- tration-dependent perturbation of anterior CNS devel- opment leading to a reduction in the size of the forcbrain, midbrain and hindbrain. In addition the overt segmental organization of the hindbrain was abolished by high concentrations of RA. The regional expression of two cell-specific markers, the homeobox protein Xhox3 and the neurotransmitter serotonin was also examined in embryos exposed to RA. Treatment with RA caused a concentration-dependent change in the pattern of expression of Xhox3 and serotonin and resulted in the ectopic appearance of immunoreactive neurons in anterior regions of the CNS, including the forebrain. Collectively, our results extend previous studies by showing that RA treatment of embryos at the neurula stage inhibits the development of anterior regions of the CNS while promoting the differentiation of more posterior cell types. The relevance of these findings to the possible role of endogenous retinoids in the determination of neural cell fate and axial patterning is discussed. Key words: axial patterning, central nervous system, embryo, retinoic acid, Xenopus laevis. Introduction The development of the embryonic vertebrate central nervous system (CNS) begins with the induction and patterning of neural ectoderm. In Xenopus embryos, induction of neural tissue from undifferentiated dorsal ectoderm is mediated by signals that derive from adjacent dorsal mesoderm during gastrulation (Spe- mann, 1938; Hamburger, 1988; Dixon and Kintner, 1989). Axial mesoderm of different anterior-posterior (A-P) character induces neural tissue of similar axial character (Mangold, 1933; Ruiz i Altaba and Melton, 19896) providing evidence that early regional differen- tiation along the A-P axis of the neural plate is controlled, in part, by dorsal mesoderm. A signal spreading through the ectoderm may also contribute to A-P patterning of the nervous system (Ruiz i Altaba, 1990). Recently, the development of the A-P axis of Xenopus embryos has been shown to be sensitive to RA (Durston et al. 1989; Sive et al. 1990; Cho and De Robertis, 1990; Ruiz i Altaba and Jessell, 1991). Application of RA to blastula and gastrula stage embryos results in the deletion of anterior structures, leading in severe cases to the complete loss of head structures (Durston et al. 1989). The microcephalic phenotype obtained after exposure of blastula and gastrula stage embryos to RA has been suggested to
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