VITAMIN-A-DEFICIENT QUAIL EMBRYOS HAVE 1 2 A HINDBRAIN AND OTHER NEURAL DEFECTS/

Background: Retinoic acid (RA) is a morphogenetically active signallin g molecule thought to be involved in the development of several embryo nic systems (based on its effect when applied in excess and the fact t hat it can be detected endogenously in embryos), Here, we adopt a nove l approach and us; the vitamin A-deficient (A(-)) quail embryo to ask what defects these embryos show when they develop in the absence of RA , with particular reference to the nervous system. Results: We have ex amined the anatomy, the expression domains of a variety of genes and t he immunoreactivity to several antibodies in these A(-) embryos. In ad dition to the previously documented cardiovascular abnormalities, we f ind that the somites are smaller in A(-) embryos, otic vesicle develop ment is abnormal and the somites continue up to and underneath the oti c vesicle, In the central nervous system, we find that neural crest ce lls need RA for normal development and survival, and the neural tube f ails to extend any neurites into the periphery. Using general hindbrai n morphology and the expression patterns of Hoxa-2, Hoxb-1, Hoxb-4, Kr ox-20 and FGF-3 as markers, we conclude that segmentation in the myele ncephalon (rhombomeres 4-8) is disrupted. In contrast, the dorsoventra l axis of the neural tube using Shh, islet-1 and Pax-3 as markers is n ormal. Conclusions: These results demonstrate at least three roles for RA in central nervous system development: neural crest survival, neur ite outgrowth and hindbrain patterning.