Investigate mechanisms of bone development in craniofacial structures of cod through pathways regulated by prostaglandins and retinoic acid

Abstract The development of craniofacial deformities is still a problem in the production of Atlantic cod (Gadus morhua) and several studies show a link between the quality of the diet and the rate of these deformities. In particular has the levels vitam in A or retinoic acid and eicosapentaenoic acid vs. arachidonic acid (the precursors for prostaglandins) been pointed out as possible causatives, but little is known about how these may affect bone development in fish, even though the mechanisms are inves tigated in terrestrial animals. The structure of bones in teleosts is quite different from terrestrial animals all though some of the signaling pathways seem to be relatively homologous. We want to investigate the development of the craniofacial structure s in cod with emphasis on gaining knowledge on how prostaglandins and retinoic acid affect the mechanisms involved through the following: 1) Establish tools: a) molecular markers for the production of prostaglandins and the pathways regulated by prostagl andins in bone and cartilage. b) cell specific markers for the classical bone cells present (osteoblasts and osteoclasts). c) A cDNA library for craniofacial structures in cod and design of an oligo microarray with genes that are regulated/regulators duri ng developmental processes d) protocols for primary cell cultures of the same cells. 2) Studies of development: a) Study the differentiation of osteoblasts and osteoclasts in primary cell cultures and effects of prostaglandins, retinoic acid and their nu tritional precursors (arachidonic acid, eicosapentaenoic acid, carotenoids and vitamin A) and antagonists. b) Study effects of the dietary arachidonic acid : eicosapentaenoic ratio and vitamin A levels on craniofacial development in start-feeding Atlantic cod, using the tools developed in 1a.