TGF-beta receptor type II and fetuin in the developing sheep neocortex

Fetuin shows a characteristic pattern of distribution in the developing neocortex in many mammalian species. Its expression is confined to early-appearing cortical-plate and later subplate neurons. A short 19 aminoacid sequence of fetuin shows a degree of homology to an 18 amino-acid sequence of the TGF-β type II receptor (TβR-II) and in vitro fetuin binds to members of the TGF-β family of cytokines. It has been suggested that fetuin is the biologically significant antagonist of these cytokines. We have compared, using immunocytochemistry, the distribution pattern of TβR-II and fetuin in the developing neocortex of foetal sheep. TβR-II immunoreactivity first appears at around 40 days of gestation in the fetal sheep (E40, term in sheep is 150 days from conception), localised in two discreet bands: one just outside the cortical plate in the inner part of the marginal zone and one deep in the cortical plate in what becomes the transient subplate zone. By E70-E80, TβR-II is prominent in a population of subplate cells, whereas, by E120 only small patches of TβR-II-positive cells are visible, principally in pyramidal cells in layer VI. The developmental sequence of the staining pattern for TβR-II in the neocortex is complementary to that for fetuin, rather than overlapping with it. Double-labelling of fetuin and TβR-II shows some cellular co-localisation, especially at E60, but most fetuin-positive cells are not immunoreactive for TβR-II. Thus, fetuin's proposed role as an antagonist of TGF-β cytokines and mimic of TβR-II is not consistent with the observed distribution of these two molecules in the developing neocortex of the foetal sheep.