Transforming growth factor-beta in neural embryogenesis and neoplasia

The transforming growth factor-beta (TGF-beta) family of polypeptides includes three structurally and functionally related mammalian isoforms that influence cell proliferation, differentiation, and extracellular matrix production. Recent identification of these isoforms in the embryonic murine central nervous system suggests that these factors may regulate proliferation and differentiation of meningeal and neuroepithelial cells during development. Predominant expression of TGF-beta 1 in the leptomeninges compared with the brain of the murine and human central nervous system implicates this isoform in regulation of that mesodermal tissue. Thus, defective TGF-beta regulation may contribute to neoplastic transformation. Failure to activate latent TGF-beta s may contribute to the loss of autocrine regulation seen in meningiomas. Expression of TGF-beta 2 and TGF-beta 3 primarily in embryonic murine radial glia and adult human astrocytes suggests other roles for these isoforms, including glioblast differentiation and guidance of neuroblast migration. Although inhibitory to "normal" astrocyte proliferation, TGF-beta s demonstrate autocrine growth stimulation in vitro among hyperdiploid malignant gliomas, medulloblastomas, primitive neuroectodermal tumors, and anaplastic ependymomas. Hence, synthesis and release of active TGF-beta s by malignant brain tumors may create aberrant stimulatory autocrine loops. The mechanism of TGF-beta-induced growth stimulation is poorly understood. Future studies will likely clarify and identify additional roles for the TGF-beta isoforms in neuro-embryogenesis and neoplasia.