Differential responses of collagen and glycosaminoglycan syntheses and cell proliferation to exogenous transforming growth factor beta 1 in the developing mouse skin fibroblasts in culture.

Skin fibroblast cultures were established from mouse foetuses at days 14, 15, 16 and 18 of gestation and from newborn mice. Modulations of mitotic and biosynthetic phenotypes of the fibroblasts by transforming growth factor beta1 (TGFbeta1) were studied. Treatment of the fibroblasts with TGFbeta1 at doses of 1 and 10 ng/ml for 48 h resulted in significant stimulation of cell proliferation in the 15-, 16- and 18-day foetal fibroblasts and a slight stimulation in the 14-day foetal fibroblasts. Treatment with TGFbeta1 resulted in stimulation of collagen synthesis approximately 2-fold in the 18-day foetal and newborn fibroblasts, but failed to stimulate it in the 14-, 15- and 16-day foetal fibroblasts. TGFbeta1 stimulated glycosaminoglycan (GAG) synthesis throughout all developmental stages approximately 1.8-2.6 fold. Histological study demonstrated that skin wounds made at day 16 of gestation were replaced with normal-appearing dermis, but at day 18 the wounds left dermal fibrosis and lack of hair follicles. These results indicate that the modulations of fibroblast phenotypes (proliferation and syntheses of collagen and GAG) in response to TGFbeta1 occur at different stages of gestation. Ontogenic transitions of skin wound healing and collagen synthetic phenotype with TGFbeta1 treatment in cultured fibroblasts occurred between days 16 and 18 of gestation, suggesting that the unresponsiveness of collagen synthesis to exogenous TGFbeta1 in cell culture may be related to the phenomenon of scarless wounds in the foetus.

Capability for reactive gliosis develops prenatally in the diencephalon but not in the cortex of rats.

In this study, the glial reactions to stab wounds were investigated on a large population of newborn (P0) and fetal rats, by the immunohistochemical staining of the glial fibrillary acidic protein. The lesions penetrated both the cortex and the diencephalon. The fetuses were lesioned in utero from the 17th embryonic day (E17) and were born on E22 or E23 in the natural way. In the cortex usually no reactive gliosis developed although definitive tissue destructions remained after the lesion. Weak and incomplete glial reactions were observed in a few cases of E20 or P0 lesions only. In the diencephalon, however, the same stabbings provoked massive glial reactions. The timing and the morphology of this reaction were similar to those found in adult animals. At E17 the lesion did not result in reactive gliosis even in the diencephalon. Our study highlights two phenomena: (i) depending on the brain area servere glial reactions can already follow fetal lesions, and (ii) the appearance of the capability for glial reactions may be a stage of the local tissue maturation in every brain area and cannot be considered as a function of brain development in general. Probably, the capability for glial reactions can take place only when certain histogenetic processes (e.g., cell migration, axon growth, apoptosis) have been at least mostly accomplished, but which of the local development events are the determining ones remains to be investigated.