Induction of a RAR beta 2-lacZ transgene by retinoic acid reflects the neuromeric organization of the central nervous system

Development ◽  
1992 ◽  
Vol 116 (4) ◽  
pp. 977-983 ◽  
Author(s):  
A. Zimmer ◽  
A. Zimmer

The hormone retinoic acid (RA) has been implicated in the organization of the anteroposterior (AP) body axis. In this paper, we describe the effects of RA on the activity of the RA-inducible retinoic acid receptor-beta 2 (RAR beta 2) promoter. When transgenic embryos carrying a RAR beta 2-lacZ reporter gene were exposed to a single dose of RA between gestational days 8.5 to 10.5, lacZ expression was induced in the anterior central nervous system (CNS). Strikingly, the transgene was expressed in a segmented pattern reminiscent of that of Drosophila ‘pair-rule’ genes. RA treatment of midgastrulation embryos at day 7.5 disturbed the segmentation and produced severe craniofacial defects. We discuss the possibility that the entire anterior CNS is segmented and that this segmentation is reflected by the RAR beta 2-lacZ induction pattern.

1993 ◽  
Vol 265 (4) ◽  
pp. R834-R839 ◽  
Author(s):  
T. Nakamori ◽  
A. Morimoto ◽  
N. Murakami

We investigated the role of central corticotropin-releasing factor (CRF) in the development of cardiovascular and thermal responses induced by stress or by interleukin-1 beta (IL-1 beta) in free-moving rats. Intracerebroventricular (icv) injection of alpha-helical CRF9-41 (10 micrograms), a CRF receptor antagonist, significantly attenuated hypertension, tachycardia, and a rise in body temperature induced by cage-switch stress, a mild stress. However, icv injection of alpha-helical CRF9-41 (10 micrograms) had no effect on hypertension, tachycardia, or fever induced by intraperitoneal (ip) injection of IL-1 beta (2 micrograms/kg) or icv prostaglandin E2 (PGE2, 100 ng). In contrast, icv injection of alpha-helical CRF9-41 (10 micrograms) significantly attenuated hypertension, tachycardia, or fever induced by icv injection of IL-1 beta (20 ng). The present results suggest that central CRF has an important role in the development of the cage-switch stress-induced responses, but it does not seem to contribute to the hypertension, tachycardia, and fever induced by ip IL-1 beta or by central PGE2. However, it is possible that when IL-1 beta directly acts on the central nervous system, some of its actions are mediated by central CRF.


1997 ◽  
Vol 86 (4) ◽  
pp. 859-865 ◽  
Author(s):  
Pamela Flood ◽  
Jose Ramirez-Latorre ◽  
Lorna Role

Background The mechanisms of action of general anesthetics are not completely understood. Many general anesthetics are reported to potentiate gamma-aminobutyric acid (GABAA) and glycine receptors in the central nervous system (CNS) and to inhibit the muscle-type nicotinic acetylcholine receptor (nAChR). The effects of general anesthetics on another family of ligand-gated ion channel in the CNS, the nAChRs, have not been defined. Methods Two types of CNS acetylcholine receptor, the alpha 4 beta 2 receptor or the alpha 7 homomeric receptor, were expressed heterologously in Xenopus laevis oocytes. Using the standard two-microelectrode voltage-clamp technique, peak acetylcholinegated current was measured before and after coapplication of isoflurane or propofol. Results Coapplication of either isoflurane or propofol with acetylcholine resulted in potent, dose-dependent inhibition of the alpha 4 beta 2 receptor current with median inhibitory concentrations of 85 and 19 microM, respectively. The inhibition of the alpha 4 beta 2 receptor by both isoflurane and propofol appears to be competitive with respect to acetylcholine. The alpha 7 receptor current was not effected by either anesthetic. Conclusions The CNS-type nAChRs are differentially affected by isoflurane and propofol. The alpha 4 beta 2 receptor is affected by isoflurane more potently than the most sensitive GABAA or glycine receptor that has been reported, whereas the alpha 7 homomeric receptor is not affected by either anesthetic. Inhibition of specific subtypes of nAChRs in the CNS, along with potentiation of GABAA and glycine receptors, may contribute to the effects and side effects of general anesthetics.


Development ◽  
1991 ◽  
Vol 112 (4) ◽  
pp. 945-958 ◽  
Author(s):  
A. Ruiz i Altaba ◽  
T.M. Jessell

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 treatment of neurula stage embryos resulted in a concentration-dependent perturbation of anterior CNS development leading to a reduction in the size of the forebrain, 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.


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