TGF-BETA RECEPTOR-TYPE-II AND FETUIN IN THE DEVELOPING SHEEP NEOCORTEX

Fetuin shows a characteristic pattern of distribution in the developin g neocortex in many mammalian species. Its expression is confined to e arly-appearing cortical-plate and later subplate neurons. A short 19 a minoacid sequence of fetuin shows a degree of homology to an 18 amino- acid sequence of the TGF-beta type II receptor (T beta R-II) and in vi tro fetuin binds to members of the TGF-beta family of cytokines. It ha s been suggested that fetuin is the biologically significant antagonis t of these cytokines. We have compared, using immunocytochemistry, the distribution pattern of T beta R-II and fetuin in the developing neoc ortex of foetal sheep. T beta R-II immunoreactivity first appears at a round 40 days of gestation in the fetal sheep (E40, term in sheep is 1 50 days from conception), localised in two discreet bands: one just ou tside the cortical plate in the inner part of the marginal zone and on e deep in the cortical plate in what becomes the transient subplate zo ne. By E70-E80, T beta R-II is prominent in a population of subplate c ells, whereas, by E120 only small patches of T beta R-II-positive cell s are visible, principally in pyramidal cells in layer VI. The develop mental sequence of the staining pattern for T beta R-II in the neocort ex is complementary to that for fetuin, rather than overlapping with i t. Double-labelling of fetuin and T beta R-II shows some cellular co-l ocalisation, especially at E60, but most fetuin-positive cells are not immunoreactive for T beta R-II. Thus, fetuin's proposed role as an an tagonist of TGF-beta cytokines and mimic of T beta R-II is not consist ent with the observed distribution of these two molecules in the devel oping neocortex of the foetal sheep.