Interactions between retinoids and TGF βs in mouse morphogenesis

Using immunocytochemical methods we describe the distribution of different TGF β isoforms and the effects of excess retinoic acid on their expression during early mouse embryogenesis ( days of development). In normal embryos at 9 days, intracellular TGF β1 is expressed most intensely in neuroepithelium and cardiac myocardium whereas extracellular TGF β1 is expressed in mesenchymal cells and in the endocardium of the heart. At later stages, intracellular TGF β1 becomes very restricted to the myocardium and to a limited number of head mesenchymal cells; extracellular TGF β1 continues to be expressed widely in cells of mesenchymal origin, particularly in head and trunk mesenchyme, and also in endocardium. TGF β1 is widely expressed at all stages investigated while TGF β3 is not expressed strongly in any tissue at the stages examined. Exposure of early neural plate stage embryos to retinoic acid caused reduced expression of TGF β1 and TGF β2 proteins but had no effect on TGF β1. Intracellular TGF β1 expression was reduced in all tissues except in the myocardium, while extracellular TGF β1 was specifically reduced in neuroepithelium and cranial neural crest cells at early stages. TGF β1 was reduced in all embryonic tissues. The down-regulation of intracellular TGF β1 was observed up to 48 hours after initial exposure to retinoic acid while some downregulation of TGF β1 was still seen up to 60 hours after initial exposure. TGF βs are known to modulate the expression of various extracellular matrix molecules involved in cell growth, differentiation and morphogenesis. The interaction between retinoic acid and TGF β is discussed in relation to morphogenesis.