What role(s) for TGF alpha in the central nervous system?

Transforming growth factor alpha (TGF alpha) is a member of the epidermal g rowth factor (EGF) family with which it shares the same receptor, the EGF r eceptor (EGFR or erbB1). Identified since 1985 in the central nervous syste m (CNS), its functions in this organ have started to be determined during t he past decade although numerous questions remain unanswered. TGF alpha is widely distributed in the nervous system, both glial and neuronal cells con tributing to its synthesis. Although astrocytes appear as its main targets, mediating in part TGF alpha. effects on different neuronal populations, re sults from different studies have raised the possibility for a direct actio n of this growth factor on neurons. A large array of experimental data have thus pointed to TGF alpha as a multifunctional factor in the CNS. This rev iew is an attempt to present, in a comprehensive manner, the very diverse w orks performed in vitro and in vivo which have provided evidences for (i) a n intervention of TGF alpha in the control of developmental events such as neural progenitors proliferation/cell fate choice, neuronal survival/differ entiation, and neuronal control of female puberty onset, (ii) its role as a potent regulator of astroglial metabolism including astrocytic reactivity, (iii) its neuroprotective potential, and (iv) its participation to neuropa thological processes as exemplified by astroglial neoplasia. In addition, i nformations regarding the complex modes of TGF alpha action at the molecula r level are provided, and its place within the large EGF family is precised with regard to the potential interactions and substitutions which may take place between TGF alpha and its kindred. (C) 2000 Elsevier Science Ltd. Al l rights reserved.