Expression of TGF-beta stimulated clone-22 (TSC-22) in mouse development and TGF-beta signalling

TSC-22 is a highly conserved member of a novel family of transcription fact ors, that is a direct target of transforming growth factor-beta (TGF-beta) in osteoblastic cells. We have investigated the expression of TSC-22 in det ail during mouse development using in situ hybridization, We detected stron g expression of TSC-22 in the embryo proper first at embryonic day 8.5 (E8. 5), in the primitive heart, intermediate mesoderm and the neural tube. The dynamics of the TSC-22 distribution in the neural tube was particularly str iking, with ubiquitous expression rostrally and restriction to neural tissu e nearer the floor plate more caudally; between E8.5 and E9.5 the zone of r estricted expression extended rostrally, At later stages of development, TS C-22 was detected in the mesenchymal compartment of many tissues and organs , including the lung, trachea, kidney, stomach, intestine, tooth buds, and in precartilage condensations. Furthermore, TSC-22 was highly expressed in the floor plate itself and notochord, and the endothelium lining the blood vessels, in particular the major arteries. Many of these sites have been pr oposed previously as possible TGF-beta target tissues; the results imply th at TSC-22 may also be a direct TGF-beta target gene during mouse embryogene sis. Experiments on TSC-22 expression in embryoid bodies of embryonic stem (ES) cells expressing dominant negative TGF-beta binding receptors initiall y supported this hypothesis. However, examination of somatic chimeras deriv ed from these same mutant ES cells at nominal E9.5 showed that TSC-22 expre ssion in the heart and neural tube was still detectable despite obvious phe notypic abnormalities. We therefore propose that although TSC-22 may be a d irect target of TGF-beta in late development, other factors are likely to b e major regulators of expression at earlier stages. (C) 2000 Wiley-Liss, In c.